Simulated dynamics and biological macromolecules

Abstract

We present a review of the use of molecular dynamics techniques to study the behaviour of proteins. The application of such methods to biological macromolecules has evolved directly from its use to study simpler physical and chemical systems. We describe the methods typically used in producing multiple nanosecond atomic trajectories. This technique is now so common that it is impossible to review the whole area. Therefore, we have focused on three areas, namely the application to proteins of biomedical importance, to folding of proteins from a random conformation to a stable well-defined tertiary structure and to the reverse process, that of unfolding. Finally, we describe some methods which have been developed to analyse complex trajectories with the aim of defining the most important features of protein dynamics and changes in conformation.

Dynamics of C60Molecules in Biological Membranes: Computer Simulation Studies

“…Such simulations have been successfully applied, for example, to enzyme reactions, protein folding, ion channels, and membrane fusion. [24][25][26][27][28][29][30][31] Computer simulation studies for the interaction between carbon nanoparticles and biological materials such as proteins and DNA have also been performed. [32][33][34][35][36][37][38] The inhibition of the HIV-1 protease by fullerenes and their derivatives 32,[36][37] was studied and the binding behavior of carbon nanotubes with nucleic acids 34,38 or amylose 33 was also investigated to improve the solubility of nanotubes.…”

Enhanced sampling by multiple molecular dynamics trajectories: carbonmonoxy myoglobin 10 μs A0 → A1–3 transition from ten 400 picosecond simulations

“…Advances in molecular dynamics [19,20] and Monte-Carlo [21] simulations have resulted in the enhanced sampling of phase space for complex biological systems [22][23][24][25][26][27][28]. Several methods attempt to probe more of the molecule's conformational space, such as the extension of the simulation to longer time periods [17,[29][30][31][32], guided enhanced sampling [33], multiple short-time trajectories [11,[34][35][36][37][38], simulated annealing [39], conformational flooding [40,41], and locally enhanced sampling [42][43][44].…”

“…Several methods attempt to probe more of the molecule's conformational space, such as the extension of the simulation to longer time periods [17,[29][30][31][32], guided enhanced sampling [33], multiple short-time trajectories [11,[34][35][36][37][38], simulated annealing [39], conformational flooding [40,41], and locally enhanced sampling [42][43][44]. In this study, we review the simulation work of multiple trajectories previously reported, [34] since recent studies indicate that this approach improves the sampling of conformational space; [11,23,[34][35][36]40,[45][46][47][48] however, a more quantitative assessment of the actual time extension has not been presented.…”

Molecular Motions of Human Cyclin-dependent Kinase 2

“…One of the best established methods for generating an ensemble from a known static structure is MD, reviewed in Ref. 17. The ensemble generated by this technique is like a movie, in that frames have a well defined temporal relationship with each other.…”