Advanced simulation techniques for the thermodynamic and kinetic characterization of biological systems

• Published in: Advances in physics: X Vol. 3; no. 1; p. 1477531
• Main Authors: Camilloni, Carlo, Pietrucci, Fabio
• Format: Journal Article
• Language: English
• Published: Taylor & Francis 01.01.2018; Taylor & Francis Group
• Subjects: 87.10.Tf 87.15.ap 07.05.Tp 87.15.A; biophysics; enhanced sampling; free-energy landscapes; kinetic models; molecular dynamics; Molecular simulation; Physics
• ISSN: 2374-6149; 2374-6149
• DOI: 10.1080/23746149.2018.1477531

This review discusses successful strategies and key open problems in the kinetic and thermodynamic characterization of complex biomolecular systems by computer simulations. The main focus is on established techniques and emerging trends in the fields of enhanced sampling and of kinetic models, as applied to biological problems ranging from protein folding and conformational dynamics to protein-protein and protein-ligand interaction. We address especially the following questions: How to choose a computational approach suited to a particular problem? What are the strengths and limitations of alternative approaches? What is the current accuracy of thermodynamic and kinetic predictions? What are today's open challenges and promising development directions? Towards the aim of accurately reproducing and interpreting experimental results, we briefly discuss hybrid approaches that combine together theoretical and experimental information. Abbreviations: CV: Collective variable. DHAM: Dynamic histogram analysis method. DoF: Degree of freedom. H-REX: Hamiltonian replica exchange. M&M: Metadynamic metainference. MetaD: Metadynamics. MD: Molecular dynamics. MSM: Markov state model. NMR: Nuclear magnetic resonance. PBMetaD: Parallel-bias metadynamics. pMaxEnt: principle of maximum entropy. PT: Parallel tempering. RECT: Replica exchange with collective-variable tempering. RMSD: Root mean square deviation. SGOOP: Spectral gap optimization of order parameters. TICA: Time-lagged independent component analysis. TRAM: Transition-based reweighing analysis method. US: Umbrella sampling. WHAM: Weighted histogram analysis method. WTMetaD: Well-tempered metadynamics.