Biomolecular simulation and modelling: status, progress and prospects

Abstract

Molecular simulation is increasingly demonstrating its practical value in the investigation of biological systems. Computational modelling of biomolecular systems is an exciting and rapidly developing area, which is expanding significantly in scope. A range of simulation methods has been developed that can be applied to study a wide variety of problems in structural biology and at the interfaces between physics, chemistry and biology. Here, we give an overview of methods and some recent developments in atomistic biomolecular simulation. Some recent applications and theoretical developments are highlighted.

Will molecular dynamics simulations of proteins ever reach equilibrium?

“…2 The ten short simulations were concatenated and the entropy was calculated for the concatenated trajectory. 3 The results of a single long simulation (380 ns for MMP12, 500 ns for the other two proteins). 4 The difference between the estimates obtained with the full trajectory and when excluding the last 100 ns of the trajectory.…”

“…They can provide an atomic-detail interpretation of biochemical process such as protein folding, enzymatic catalysis, and molecular recognition. 1,2,3 The quantity that drives these reactions is the free energy, ΔG, and computational methods to estimate it for various processes can be derived from the laws of statistical mechanics. 4,5 However, it is also often of interest to decompose the free energy into enthalpic (ΔH) and entropic (ΔS) parts to obtain additional insight into the process, according to…”

Less is more when simulating unsulfated glycosaminoglycan 3D‐structure: Comparison of GLYCAM06/TIP3P, PM3‐CARB1/TIP3P, and SCC‐DFTB‐D/TIP3P predictions with experiment

“…However, many semi-empirical methods have not performed well for glycosaminoglycans. 21,22 Among the most promising approaches are PM3-CARB1 23 (a re-parameterization of PM3 24 for carbohydrates) and the self-consistent charge density functional tightbinding method 25 (SCC-DFTB-D), an approximate method based on a second-order expansion of the DFT total energy expression and including an empirical energetic correction for dispersion. The efficiency of such methods (compared with DFT) stems from usage of a minimal basis.…”

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

“…Computational studies can provide a complementary tool to help elucidate some of the outstanding questions. In the last decade, computer simulation of biomolecules, in particular proteins, has advanced significantly [26]. A method that has had a particularly large impact is molecular dynamics (MD) simulation.…”