Abstract
The proper folding of a protein is essential for its biological functions. Thermal denaturation of protein structure has been used as an essential tool to understand the unfolding mechanism and measure thermodynamic stability. New technologies have made it feasible to heat proteins using femtosecond laser technology and nanoparticle-targeting methods locally. It is crucial to comprehend how quickly proteins can unfold or lose their function at high temperatures. Protein folding and unfolding have been widely modelled using molecular dynamics (MD) simulations. MD simulations provide information about protein folding that is otherwise impractical through experimental approaches. Techniques like targeted molecular dynamics (TMD) simulations and acid-thermal denaturation correspond to varying degrees of success with experimental observations. These simulations, utilized in tandem with experiments, provide crucial information on the protein folding mechanism. Because of recent computer hardware and software improvements, it is now possible to include a broad range of temperature factors in thermal denaturation studies. In this chapter, we dwell on these details and discuss the thermal unfolding of proteins and their applications. Various computational methods and tools and their uses in protein folding/unfolding studies are described. We also cover an overview of limitations, significant contributions, and recent advancements in MD simulation approaches to study protein folding.
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References
J.C. Whisstock, A.M. Lesk, Prediction of protein function from protein sequence and structure. Q. Rev. Biophys. 36(3), 307–340 (2003)
D.B. Singh, T. Tripathi, Frontiers in Protein Structure, Function, and Dynamics (Springer Nature, Singapore, 2020)
P. Davis, S. Williams, Protein modification by thermal processing. Allergy 53, 102–105 (1998)
R. Jaenicke, Protein folding: local structures, domains, subunits, and assemblies. Biochemistry 30(13), 3147–3161 (1991)
H. Wu, Studies on denaturation of proteins XIII. A theory of denaturation. Adv. Protein Chem. 46, 6–26 (1995)
V.N. Uversky, N.V. Narizhneva, S.O. Kirschstein, S. Winter, G. Löber, Conformational transitions provoked by organic solvents in β-lactoglobulin: can a molten globule like intermediate be induced by the decrease in dielectric constant? Fold. Des. 2(3), 163–172 (1997)
C.M. Dobson, M. Karplus, The fundamentals of protein folding: bringing together theory and experiment. Curr. Opin. Struct. Biol. 9(1), 92–101 (1999)
D. Thirumalai, E.P. O’Brien, G. Morrison, C. Hyeon, Theoretical perspectives on protein folding. Annu. Rev. Biophys. 39, 159–183 (2010)
P. Saudagar, T. Tripathi, Advanced Spectroscopic Methods to Study Biomolecular Structure and Dynamics, 1st edn. (Academic Press, San Diego, 2023)
T. Tripathi, V.K. Dubey, Advances in Protein Molecular and Structural Biology Methods, 1st edn. (Academic Press, Cambridge, MA, 2022)
S.E. Radford, Protein folding: progress made and promises ahead. Trends Biochem. Sci. 25(12), 611–618 (2000)
J. Yon, Protein folding: a perspective for biology, medicine and biotechnology. Braz. J. Med. Biol. Res. 34, 419–435 (2001)
A. Gershenson, S. Gosavi, P. Faccioli, P.L. Wintrode, Successes and challenges in simulating the folding of large proteins. J. Biol. Chem. 295(1), 15–33 (2020)
R. Lazim, D. Suh, S. Choi, Advances in molecular dynamics simulations and enhanced sampling methods for the study of protein systems. Int. J. Mol. Sci. 21(17), 6339 (2020)
D. Bhowmik, S. Gao, M.T. Young, A. Ramanathan, Deep clustering of protein folding simulations. BMC Bioinformatics 19(18), 47–58 (2018)
A.R. Fersht, V. Daggett, Protein folding and unfolding at atomic resolution. Cell 108(4), 573–582 (2002)
V. Daggett, Protein folding-simulation. Chem. Rev. 106(5), 1898–1916 (2006)
A. Prakash, D. Idrees, M.A. Haque, A. Islam, F. Ahmad, M.I. Hassan, GdmCl-induced unfolding studies of human carbonic anhydrase IX: a combined spectroscopic and MD simulation approach. J. Biomol. Struct. Dyn. 35(6), 1295–1306 (2017)
H. Naz, M. Shahbaaz, M.A. Haque, K. Bisetty, A. Islam, F. Ahmad, M.I. Hassan, Urea-induced denaturation of human calcium/calmodulin-dependent protein kinase IV: a combined spectroscopic and MD simulation studies. J. Biomol. Struct. Dyn. 35(3), 463–475 (2017)
D. Idrees, S. Rahman, M. Shahbaaz, M.A. Haque, A. Islam, F. Ahmad, M.I. Hassan, Estimation of thermodynamic stability of human carbonic anhydrase IX from urea-induced denaturation and MD simulation studies. Int. J. Biol. Macromol. 105, 183–189 (2017)
D. Idrees, A. Prakash, M.A. Haque, A. Islam, F. Ahmad, M.I. Hassan, Spectroscopic and MD simulation studies on unfolding processes of mitochondrial carbonic anhydrase VA induced by urea. J. Biomol. Struct. Dyn. 34(9), 1987–1997 (2016)
A.A.T. Naqvi, T. Mohammad, G.M. Hasan, M.I. Hassan, Advancements in docking and molecular dynamics simulations towards ligand-receptor interactions and structure-function relationships. Curr. Top. Med. Chem. 18(20), 1755–1768 (2018)
A.A.T. Naqvi, U. Kiran, M.Z. Abdin, M.I. Hassan, Bioinformatic tools to understand structure and function of plant proteins, in Transgenic Technology Based Value Addition in Plant Biotechnology, (Academic Press, San Diego, 2020), pp. 69–93
R. Day, V. Daggett, All-atom simulations of protein folding and unfolding. Adv. Protein Chem. 66, 373–403 (2003)
R. Day, V. Daggett, Ensemble versus single-molecule protein unfolding. Proc. Natl. Acad. Sci. 102(38), 13445–13450 (2005)
F.I. Khan, P. Gupta, S. Roy, N. Azum, K.A. Alamry, A.M. Asiri, D. Lai, M.I. Hassan, Mechanistic insights into the urea-induced denaturation of human sphingosine kinase 1. Int. J. Biol. Macromol. 161, 1496–1505 (2020)
F.I. Khan, K. Bisetty, S. Singh, K. Permaul, M.I. Hassan, Chitinase from thermomyces lanuginosus SSBP and its biotechnological applications. Extremophiles 19(6), 1055–1066 (2015)
F.I. Khan, K. Bisetty, K.R. Gu, S. Singh, K. Permaul, M.I. Hassan, D.Q. Wei, Molecular dynamics simulation of chitinase I from thermomyces lanuginosus SSBP to ensure optimal activity. Mol. Simul. 43(7), 480–490 (2017)
F.I. Khan, S. Ali, W. Chen, F. Anjum, A. Shafie, M.I. Hassan, D. Lai, High-resolution MD simulation studies to get mechanistic insights into the urea-induced denaturation of human sphingosine kinase 1. Curr. Top. Med. Chem. 21(31), 2839–2850 (2021)
P.G. Wolynes, Evolution, energy landscapes and the paradoxes of protein folding. Biochimie 119, 218–230 (2015)
X. Periole, A.E. Mark, Convergence and sampling efficiency in replica exchange simulations of peptide folding in explicit solvent. J. Chem. Phys. 126(1), 01B601 (2007)
H. Lei, Y. Duan, Improved sampling methods for molecular simulation. Curr. Opin. Struct. Biol. 17(2), 187–191 (2007)
K. Ostermeir, M. Zacharias, Advanced replica-exchange sampling to study the flexibility and plasticity of peptides and proteins. Biochim. Biophys. Acta 1834(5), 847–853 (2013)
Y.M. Rhee, V.S. Pande, Multiplexed-replica exchange molecular dynamics method for protein folding simulation. Biophys. J. 84(2), 775–786 (2003)
R. Zhou, Replica exchange molecular dynamics method for protein folding simulation, in Protein Folding Protocols, (Springer, Cham, 2007), pp. 205–223
R. Shukla, T. Tripathi, Molecular dynamics simulation of protein and protein-ligand complexes, in Computer-Aided Drug Design, ed. by D.B. Singh, (Springer Nature, Singapore, 2020), pp. 133–161
R. Shukla, T. Tripathi, Molecular dynamics simulation in drug discovery: opportunities and challenges, in Innovations and Implementations of Drug Discovery Strategies in Rational Drug Design, ed. by S.K. Singh, (Springer Nature, Singapore, 2021), pp. 295–316
S. Robic, Mathematics, thermodynamics, and modeling to address ten common misconceptions about protein structure, folding, and stability. CBE Life Sci. Educ. 9(3), 189–195 (2010)
K. Anwer, R. Sonani, D. Madamwar, P. Singh, F. Khan, K. Bisetty, F. Ahmad, M.I. Hassan, Role of N-terminal residues on folding and stability of C-phycoerythrin: simulation and urea-induced denaturation studies. J. Biomol. Struct. Dyn. 33(1), 121–133 (2015)
K. Anwer, S. Rahman, R.R. Sonani, F.I. Khan, A. Islam, D. Madamwar, F. Ahmad, M.I. Hassan, Probing pH sensitivity of αC-phycoerythrin and its natural truncant: a comparative study. Int. J. Biol. Macromol. 86, 18–27 (2016)
K. Anwer, A. Parmar, S. Rahman, A. Kaushal, D. Madamwar, A. Islam, M.I. Hassan, F. Ahmad, Folding and stability studies on C-PE and its natural N-terminal truncant. Arch. Biochem. Biophys. 545, 9–21 (2014)
G.N. Somero, Proteins and temperature. Annu. Rev. Physiol. 57(1), 43–68 (1995)
V.Y. Alexandrov, Conformational flexibility of proteins, their resistance to proteinases and temperature conditions of life. Biosystems 3(1), 9–19 (1969)
T. Tripathi, Calculation of thermodynamic parameters of protein unfolding using far-ultraviolet circular dichroism. J. Protein. Proteomics 4(2), 85–91 (2013)
R. Jaenicke, Protein structure and function at low temperatures. Philos. Trans. R. Soc. Lond. B Biol. Sci. 326(1237), 535–553 (1990)
S. Bondos, K. Matthews, Protein Folding (McGraw-Hill, New York, 2021)
H.J. Dyson, P.E. Wright, Intrinsically unstructured proteins and their functions. Nat. Rev. Mol. Cell Biol. 6(3), 197–208 (2005)
A.G. Rocco, L. Mollica, P. Ricchiuto, A.M. Baptista, E. Gianazza, I. Eberini, Characterization of the protein unfolding processes induced by urea and temperature. Biophys. J. 94(6), 2241–2251 (2008)
A. Arsiccio, J.E. Shea, Pressure unfolding of proteins: new insights into the role of bound water. J. Phys. Chem. B 125(30), 8431–8442 (2021)
L.J. Lapidus, Protein unfolding mechanisms and their effects on folding experiments. F1000Res 6, 1723 (2017)
R. Day, B.J. Bennion, S. Ham, V. Daggett, Increasing temperature accelerates protein unfolding without changing the pathway of unfolding. J. Mol. Biol. 322(1), 189–203 (2002)
A. Caflisch, M. Karplus, Molecular dynamics simulation of protein denaturation: solvation of the hydrophobic cores and secondary structure of barnase. Proc. Natl. Acad. Sci. 91(5), 1746–1750 (1994)
J.A. McCammon, B.R. Gelin, M. Karplus, Dynamics of folded proteins. Nature 267(5612), 585–590 (1977)
M. Pechlaner, W.F. van Gunsteren, N. Hansen, L.J. Smith, Molecular dynamics simulation or structure refinement of proteins: are solvent molecules required? A case study using hen lysozyme. Eur. Biophys. J. 51(3), 265–282 (2022)
K. Lindorff-Larsen, P. Maragakis, S. Piana, M.P. Eastwood, R.O. Dror, D.E. Shaw, Systematic validation of protein force fields against experimental data. PLoS One 7(2), e32131 (2012)
V. Daggett, A. Fersht, The present view of the mechanism of protein folding. Nat. Rev. Mol. Cell Biol. 4(6), 497–502 (2003)
A. Sonkar, D.L. Lyngdoh, R. Shukla, H. Shukla, T. Tripathi, S. Ahmed, Point mutation A394E in the central intrinsic disordered region of Rna14 leads to chromosomal instability in fission yeast. Int. J. Biol. Macromol. 119, 785–791 (2018)
J. Kalita, R. Shukla, T. Tripathi, Structural basis of urea-induced unfolding of Fasciola gigantica glutathione S-transferase. J. Cell. Physiol. 234(4), 4491–4503 (2019)
P.B. Chetri, R. Shukla, T. Tripathi, Identification and characterization of cytosolic malate dehydrogenase from the liver fluke Fasciola gigantica. Sci. Rep. 10(1), 13372 (2020)
U. Mayor, C.M. Johnson, V. Daggett, A.R. Fersht, Protein folding and unfolding in microseconds to nanoseconds by experiment and simulation. Proc. Natl. Acad. Sci. 97(25), 13518–13522 (2000)
U. Mayor, N.R. Guydosh, C.M. Johnson, J.G. Grossmann, S. Sato, G.S. Jas, S. Freund, D.O. Alonso, V. Daggett, A.R. Fersht, The complete folding pathway of a protein from nanoseconds to microseconds. Nature 421(6925), 863–867 (2003)
H.J.C. Berendsen, J.P.M. Postma, W.F. van Gunsteren, A. DiNola, J.R. Haak, Molecular dynamics with coupling to an external bath. J. Chem. Phys. 81, 3684–3690 (1984)
J.E. Basconi, M.R. Shirts, Effects of temperature control algorithms on transport properties and kinetics in molecular dynamics simulations. J. Chem. Theory Comput. 9(7), 2887–2899 (2013)
M.R. Shirts, Simple quantitative tests to validate sampling from thermodynamic ensembles. J. Chem. Theory Comput. 9(2), 909–926 (2013)
H.C. Andersen, Molecular dynamics simulations at constant pressure and/or temperature. J. Chem. Phys. 72, 2384–2393 (1980)
E.A. Koopman, C.P. Lowe, Advantages of a Lowe-Andersen thermostat in molecular dynamics simulations. J. Chem. Phys. 124(20), 204103 (2006)
G. Bussi, D. Donadio, M. Parrinello, Canonical sampling through velocity rescaling. J. Chem. Phys. 126(1), 014101 (2007)
S. Nosé, A molecular dynamics method for simulations in the canonical ensemble. Mol. Phys. 52, 255–268 (1984)
W.G. Hoover, Canonical dynamics: equilibrium phase-space distributions. Phys. Rev. A Gen. Phys. 31(3), 1695–1697 (1985)
M.L.K. Glenn, J. Martyna, Nosé–Hoover chains: the canonical ensemble via continuous dynamics. J. Chem. Phys. 97, 2635–2643 (1992)
S. Roy, T. Mohammad, P. Gupta, R. Dahiya, S. Parveen, S. Luqman, G.M. Hasan, M.I. Hassan, Discovery of harmaline as a potent inhibitor of sphingosine kinase-1: a chemopreventive role in lung cancer. ACS Omega 5(34), 21550–21560 (2020)
F. Naz, F.I. Khan, T. Mohammad, P. Khan, S. Manzoor, G.M. Hasan, K.A. Lobb, S. Luqman, A. Islam, F. Ahmad, M.I. Hassan, Investigation of molecular mechanism of recognition between citral and MARK4: a newer therapeutic approach to attenuate cancer cell progression. Int. J. Biol. Macromol. 107(Pt B), 2580–2589 (2018)
T. Mohammad, S. Siddiqui, A. Shamsi, M.F. Alajmi, A. Hussain, A. Islam, F. Ahmad, M.I. Hassan, Virtual screening approach to identify high-affinity inhibitors of serum and glucocorticoid-regulated kinase 1 among bioactive natural products: combined molecular docking and simulation studies. Molecules 25(4), 823 (2020)
T. Mohammad, M. Amir, K. Prasad, S. Batra, V. Kumar, A. Hussain, M.T. Rehman, M.F. AlAjmi, M.I. Hassan, Impact of amino acid substitution in the kinase domain of Bruton tyrosine kinase and its association with X-linked agammaglobulinemia. Int. J. Biol. Macromol. 164, 2399–2408 (2020)
S. Fatima, T. Mohammad, D.S. Jairajpuri, M.T. Rehman, A. Hussain, M. Samim, F.J. Ahmad, M.F. Alajmi, M.I. Hassan, Identification and evaluation of glutathione conjugate gamma-l-glutamyl-l-cysteine for improved drug delivery to the brain. J. Biomol. Struct. Dyn. 38(12), 3610–3620 (2020)
V.N. Maiorov, G.M. Crippen, Significance of root-mean-square deviation in comparing three-dimensional structures of globular proteins. J. Mol. Biol. 235(2), 625–634 (1994)
A. Bagaria, V. Jaravine, Y.J. Huang, G.T. Montelione, P. Güntert, Protein structure validation by generalized linear model root-mean-square deviation prediction. Protein Sci. 21(2), 229–238 (2012)
M. Purmonen, J. Valjakka, K. Takkinen, T. Laitinen, J. Rouvinen, Molecular dynamics studies on the thermostability of family 11 xylanases. Protein Eng. Des. Sel. 20(11), 551–559 (2007)
S. Fenwick, S.K. Vanga, A. DiNardo, J. Wang, V. Raghavan, A. Singh, Computational evaluation of the effect of processing on the trypsin and alpha-amylase inhibitor from Ragi (Eleusine coracana) seed. Eng. Rep. 1(4), e12064 (2019)
K. Kobayashi, M.U. Salam, Comparing simulated and measured values using mean squared deviation and its components. Agron. J. 92(2), 345–352 (2000)
A. Cooper, Thermodynamic fluctuations in protein molecules. Proc. Natl. Acad. Sci. 73(8), 2740–2741 (1976)
S.L. Rath, M. Tripathy, N. Mandal, How does temperature affect the dynamics of SARS-CoV-2 M proteins? Insights from molecular dynamics simulations. J. Membr. Biol. 255, 341–356 (2022)
I. Sarkar, A. Sen, In silico screening predicts common cold drug dextromethorphan along with prednisolone and dexamethasone can be effective against novel coronavirus disease (COVID-19). J. Biomol. Struct. Dyn. 40(8), 3706–3710 (2022)
A. Kuzmanic, B. Zagrovic, Determination of ensemble-average pairwise root mean-square deviation from experimental B-factors. Biophys. J. 98(5), 861–871 (2010)
N.N. Cob-Calan, L.A. Chi-Uluac, F. Ortiz-Chi, D. Cerqueda-GarcÃa, G. Navarrete-Vázquez, E. Ruiz-Sánchez, E. Hernández-Núñez, Molecular docking and dynamics simulation of protein β-tubulin and antifungal cyclic lipopeptides. Molecules 24(18), 3387 (2019)
J.A. Ippolito, R.S. Alexander, D.W. Christianson, Hydrogen bond stereochemistry in protein structure and function. J. Mol. Biol. 215(3), 457–471 (1990)
W.B. Cardoso, S.A. Mendanha, Molecular dynamics simulation of docking structures of SARS-CoV-2 main protease and HIV protease inhibitors. J. Mol. Struct. 1225, 129143 (2021)
M.S. Weiss, M. Brandl, J. Sühnel, D. Pal, R. Hilgenfeld, More hydrogen bonds for the (structural) biologist. Trends Biochem. Sci. 26(9), 521–523 (2001)
Z. Bikadi, L. Demko, E. Hazai, Functional and structural characterization of a protein based on analysis of its hydrogen bonding network by hydrogen bonding plot. Arch. Biochem. Biophys. 461(2), 225–234 (2007)
I. Habib, S. Khan, T. Mohammad, A. Hussain, M.F. Alajmi, T. Rehman, F. Anjum, M.I. Hassan, Impact of non-synonymous mutations on the structure and function of telomeric repeat binding factor 1. J. Biomol. Struct. Dyn. 40(19), 9053–9066 (2022)
P. Gupta, T. Mohammad, P. Khan, M.F. Alajmi, A. Hussain, M.T. Rehman, M.I. Hassan, Evaluation of ellagic acid as an inhibitor of sphingosine kinase 1: a targeted approach towards anticancer therapy. Biomed. Pharmacother. 118(109245), 25 (2019)
P. Gupta, T. Mohammad, R. Dahiya, S. Roy, O.M.A. Noman, M.F. Alajmi, A. Hussain, M.I. Hassan, Evaluation of binding and inhibition mechanism of dietary phytochemicals with sphingosine kinase 1: towards targeted anticancer therapy. Sci. Rep. 9(1), 019–55199 (2019)
M. Amir, T. Mohammad, V. Kumar, M.F. Alajmi, M.T. Rehman, A. Hussain, P. Alam, R. Dohare, A. Islam, F. Ahmad, M.I. Hassan, Structural analysis and conformational dynamics of STN1 gene mutations involved in coat plus syndrome. Front. Mol. Biosci. 6, 41 (2019)
M.F. AlAjmi, S. Khan, A. Choudhury, T. Mohammad, S. Noor, A. Hussain, W. Lu, M.S. Eapen, V. Chimankar, P.M. Hansbro, S.S. Sohal, A.M. Elasbali, M.I. Hassan, Impact of deleterious mutations on structure, function and stability of serum/glucocorticoid regulated kinase 1: a gene to diseases correlation. Front. Mol. Biosci. 8, 780284 (2021)
M. Adnan, S. Koli, T. Mohammad, A.J. Siddiqui, M. Patel, N. Alshammari, F. Bardakci, A.M. Elasbali, M.I. Hassan, Searching for novel anaplastic lymphoma kinase inhibitors: structure-guided screening of natural compounds for a tyrosine kinase therapeutic target in cancers. OMICS 26(8), 461–470 (2022)
W. Li, J. Ma, S. Wu, J. Zhang, J. Cheng, The effect of hydrogen bond on the thermal and mechanical properties of furan epoxy resins: molecular dynamics simulation study. Polym. Test. 101, 107275 (2021)
Y. Gao, Y. Mei, J. Zhang, Treatment of hydrogen bonds in protein simulations, in Advanced Materials for Renewable Hydrogen Production, Storage and Utilization, (InTech, London, 2015), pp. 121–136
D. Pantoja-Uceda, M.T. Pastor, J. Salgado, A. Pineda-Lucena, E. Pérez-Payá, Design of a bivalent peptide with two independent elements of secondary structure able to fold autonomously. J. Pept. Sci. 14(7), 845–854 (2008)
S. Zhang, N. Yuan, W. Li, C. Wang, F. Li, J. Xu, T. Suo, A close look at the conformational transitions of a helical polymer in its response to environmental stimuli. AIP Adv. 11(8), 085107 (2021)
J.J. Tanner, Empirical power laws for the radii of gyration of protein oligomers. Acta Crystallogr. D Struct. Biol. 72(10), 1119–1129 (2016)
S. Ghahremanian, M.M. Rashidi, K. Raeisi, D. Toghraie, Molecular dynamics simulation approach for discovering potential inhibitors against SARS-CoV-2: a structural review. J. Mol. Liq. 354, 118901 (2022)
M.Y. Lobanov, N. Bogatyreva, O. Galzitskaya, Radius of gyration as an indicator of protein structure compactness. Mol. Biol. 42(4), 623–628 (2008)
D. Li, H.-T. Li, H. Wu, Y. Wang, Using the group contribution method and molecular dynamics to predict the glass transition temperatures and mechanical properties of poly-(p-phenylenediamine-alt-2, 6-diformyl multiphenyl). J. Chem. Res. 45(9-10), 823–830 (2021)
S. Ausaf Ali, I. Hassan, A. Islam, F. Ahmad, A review of methods available to estimate solvent-accessible surface areas of soluble proteins in the folded and unfolded states. Curr. Protein Pept. Sci. 15(5), 456–476 (2014)
J.A. Marsh, S.A. Teichmann, Relative solvent accessible surface area predicts protein conformational changes upon binding. Structure 19(6), 859–867 (2011)
M. Moret, G. Zebende, Amino acid hydrophobicity and accessible surface area. Phys. Rev. E 75(1), 011920 (2007)
S. Sivakumar, M. Mohan, O. Franco, B. Thayumanavan, Inhibition of insect pest α-amylases by little and finger millet inhibitors. Pestic. Biochem. Physiol. 85(3), 155–160 (2006)
B. Lee, F.M. Richards, The interpretation of protein structures: estimation of static accessibility. J. Mol. Biol. 55(3), 379–400 (1971)
S.L. Rath, K. Kumar, Investigation of the effect of temperature on the structure of SARS-Cov-2 spike protein by molecular dynamics simulations. Front. Mol. Biosci. 7, 583523 (2020)
G.G. Maisuradze, A. Liwo, H.A. Scheraga, Principal component analysis for protein folding dynamics. J. Mol. Biol. 385(1), 312–329 (2009)
C.C. David, D.J. Jacobs, Principal component analysis: a method for determining the essential dynamics of proteins. Methods Mol. Biol. 1084, 193–226 (2014)
G.G. Maisuradze, A. Liwo, H.A. Scheraga, Relation between free energy landscapes of proteins and dynamics. J. Chem. Theory Comput. 6(2), 583–595 (2010)
B. Borges, G. Gallo, C. Coelho, N. Negri, F. Maiello, L. Hardy, M. Würtele, Dynamic cross correlation analysis of thermus thermophilus alkaline phosphatase and determinants of thermostability. Biochim. Biophys. Acta 1865(7), 129895 (2021)
S. Kumar, P.A. Deshpande, Structural and thermodynamic analysis of factors governing the stability and thermal folding/unfolding of SazCA. PLoS One 16(4), e0249866 (2021)
Z. Chen, Y. Fu, W. Xu, M. Li, Molecular dynamics simulation of barnase: contribution of noncovalent intramolecular interaction to thermostability. Math. Probl. Eng. 2013, 504183 (2013)
W. Gu, T. Wang, J. Zhu, Y. Shi, H. Liu, Molecular dynamics simulation of the unfolding of the human prion protein domain under low pH and high temperature conditions. Biophys. Chem. 104(1), 79–94 (2003)
E.R. Henry, R.B. Best, W.A. Eaton, Comparing a simple theoretical model for protein folding with all-atom molecular dynamics simulations. Proc. Natl. Acad. Sci. U S A 110(44), 17880–17885 (2013)
D.B. Singh, R.K. Pathak, Bioinformatics: Methods and Applications (Academic Press, San Diego, 2021)
S. Piana, J.L. Klepeis, D.E. Shaw, Assessing the accuracy of physical models used in protein-folding simulations: quantitative evidence from long molecular dynamics simulations. Curr. Opin. Struct. Biol. 24, 98–105 (2014)
S.A. Hollingsworth, R.O. Dror, Molecular dynamics simulation for all. Neuron 99(6), 1129–1143 (2018)
D.A. Beck, V. Daggett, Methods for molecular dynamics simulations of protein folding/unfolding in solution. Methods 34(1), 112–120 (2004)
J. Ferina, V. Daggett, Visualizing protein folding and unfolding. J. Mol. Biol. 431(8), 1540–1564 (2019)
L. Duan, X. Guo, Y. Cong, G. Feng, Y. Li, J.Z.H. Zhang, Accelerated molecular dynamics simulation for helical proteins folding in explicit water. Front. Chem. 7, 540 (2019)
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M.I.H. thanks the Council of Scientific and Industrial Research for financial support [Project No. 27(0368)/20/EMR-II].
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Hassan, M.I. et al. (2023). Molecular Dynamics Simulation to Study Thermal Unfolding in Proteins. In: Saudagar, P., Tripathi, T. (eds) Protein Folding Dynamics and Stability. Springer, Singapore. https://doi.org/10.1007/978-981-99-2079-2_12
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