Conformational flexibility and generalized structural features are responsible for specific phenomena existing in biological pathways. With advancements in computational chemistry, novel approaches and new methods are required to compare the dynamic nature of biomolecules, which are crucial not only to address dynamic functional relationships but also to gain detailed insights into the disturbance and positional fluctuation responsible for functional shifts. Keeping this in mind, axial frequency distribution (AFD) has been developed, designed, and implemented. AFD can profoundly represent distribution and density of ligand atom around a particular atom or set of atoms. It enabled us to obtain an explanation of local movements and rotations, which are not significantly highlighted by any other structural and dynamical parameters. AFD can be implemented on biological models representing ligand and protein interactions. It shows a comprehensive view of the binding pattern of ligand by exploring the distribution of atoms relative to the x-y plane of the system. By taking a relative centroid on protein or ligand, molecular interactions like hydrogen bonds, van der Waals, polar or ionic interaction can be analyzed to cater the ligand movement, stabilization or flexibility with respect to the protein. The AFD graph resulted in the residual depiction of bi-molecular interaction in gradient form which can yield specific information depending upon the system of interest.
Molecular dynamics simulation Conformational analysis Software Axial frequency distribution Radial distribution function Binding pattern
This is a preview of subscription content, log in to check access.
The authors would like to acknowledge the valuable insight and testing done by Klaus R. Liedl and Julian E. Fuch at Theoretical Chemistry, Faculty of Chemistry and Pharmacy, Center for Molecular Biosciences, Leopold-Franzens-University Innsbruck. The authors would also like to acknowledge Higher Education Commission, Pakistan, International Foundation for Science and Ernst Mach follow-up grant for financial assistance.
SSA designed, conceived and drafted the manuscript. SR programmed and debugged the software and also drafted the manuscript.
Boehr DD, Nussinov R, Wright PE (2009) The role of dynamic conformational ensembles in biomolecular recognition. Nat Chem Biol 5:789–796CrossRefGoogle Scholar
Grossman M, Born B, Heyden M et al (2011) Correlated structural kinetics and retarded solvent dynamics at the metalloprotease active site. Nat Struct Mol Biol 18:1102–1108CrossRefGoogle Scholar
Buch I, Giorgino T, De Fabritiis G (2011) Complete reconstruction of an enzyme-inhibitor binding process by molecular dynamics simulations. Proc Natl Acad Sci 108:10184–10189CrossRefGoogle Scholar
Clore GM, Schwieters CD (2004) Amplitudes of protein backbone dynamics and correlated motions in a small α/β protein: correspondence of dipolar coupling and heteronuclear relaxation measurements. Biochemistry 43:10678–10691CrossRefGoogle Scholar
Salmon L, Yang S, Al-Hashimi HM (2014) Advances in the determination of nucleic acid conformational ensembles. Annu Rev Phys Chem 65:293CrossRefGoogle Scholar
Lindorff-Larsen K, Best RB, DePristo MA et al (2005) Simultaneous determination of protein structure and dynamics. Nature 433:128–132CrossRefGoogle Scholar
Karplus M, McCammon JA (2002) Molecular dynamics simulations of biomolecules. Nat Struct Mol Biol 9:646–652CrossRefGoogle Scholar
Donohue J (1954) Radial distribution functions of some structures of the polypeptide chain. Proc Natl Acad Sci U S A 40:377CrossRefGoogle Scholar
Azam SS, Abro A, Raza S (2015) Binding pattern analysis and structural insight into the inhibition mechanism of sterol 24-C methyltransferase by docking and molecular dynamics approach. J Biomol Struct Dyn 33:2563–2577CrossRefGoogle Scholar
Abbasi S, Raza S, Azam SS et al (2016) Interaction mechanisms of a melatonergic inhibitor in the melatonin synthesis pathway. J Mol Liq 221:507–517CrossRefGoogle Scholar
Ul Haq F, Abro A, Raza S et al (2017) Molecular dynamics simulation studies of novel β-lactamase inhibitor. J Mol Graph Model 74:143–152CrossRefGoogle Scholar
Ahmad S, Raza S, Uddin R, Azam SS (2017) Binding mode analysis, dynamic simulation and binding free energy calculations of the MurF ligase from Acinetobacter baumannii. J Mol Graph Model 77:72-85Google Scholar
Azam SS, Abro A, Raza S, Saroosh A (2014) Structure and dynamics studies of sterol 24-C-methyltransferase with mechanism based inactivators for the disruption of ergosterol biosynthesis. Mol Biol Rep 41:4279–4293CrossRefGoogle Scholar
Jeffrey GA (1997) An introduction to hydrogen bonding. J Am Chem Soc 120:5604–5604Google Scholar
Wallace AC, Laskowski RA, Thornton JM (1995) LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng 8:127–134CrossRefGoogle Scholar