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Enhanced Sampling and Free Energy Methods to Study Protein Folding and Dynamics

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Protein Folding Dynamics and Stability

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Abstract

A virtual study of the physical and chemical behaviour of particles in the energy space is referred to as computer simulation. The interaction of biomolecules and atoms during conformational changes is studied through molecular dynamics (MD) simulation. MD simulation complements the experimental results by providing a theoretical perspective of the real-time environment. However, the sampling of configuration is limited to a definite timescale due to free energy barriers. This free energy barrier arises due to the energy gap between initial and closing entropy in biomolecular structural transition. To deal with this biophysical problem, various enhanced sampling methods have been developed that are classified into collective variable-based and collective variable-free approaches based on the algorithm of the sampling method. This chapter discusses the numerical aspects of sampling methods, followed by a review of some of the most commonly used techniques in MD simulation and enhanced sampling. Lastly, a combined enhanced sampling method has been discussed.

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Acknowledgements

The authors acknowledge the research facility provided by Alagappa University. The authors also thank the Department of Biotechnology (DBT-BIC) Project Grant/Award (No.BT/PR40154/BTIS/137/34/2021), RUSA-Phase 2.0 Policy (TNmulti-Gen), Dept. of Edn, Govt. of India (Grant No: F.24-51/2014-U), Department of Biotechnology (DBT), New Delhi Grant/Award (No.BT/PR40154/BTIS/137/34/2021), The Higher Education, Govt. of Tamil Nadu for the Grant (No. 5594/H1/2020-1), The Tamil Nadu State Council for Higher Education (TANSCHE) for the research grant (Au/S.o. (P&D): TANSCHE Projects: 117/2021), DST-PURSE 2nd Phase Programme Order no. SR/PURSE phase 2/28 (G dated 21.02.2017) and FIST (SR/FST/LSI—667/2016) for financial support.

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Authors and Affiliations

  1. Department of Bioinformatics, Alagappa University, Karaikudi, Tamilnadu, India

    Muthuraja Arun Pravin & Sanjeev Kumar Singh

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  1. Muthuraja Arun Pravin
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  2. Sanjeev Kumar Singh
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Editors and Affiliations

  1. Department of Biotechnology, National Institute of Technology, Warangal, Telangana, India

    Prakash Saudagar

  2. Department of Biochemistry, North-Eastern Hill University, Shillong, Meghalaya, India

    Timir Tripathi

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Pravin, M.A., Singh, S.K. (2023). Enhanced Sampling and Free Energy Methods to Study Protein Folding and Dynamics. In: Saudagar, P., Tripathi, T. (eds) Protein Folding Dynamics and Stability. Springer, Singapore. https://doi.org/10.1007/978-981-99-2079-2_9

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