Monte-Carlo and molecular dynamics modelling of biopolymers, DNA, proteins and molecular motors
The mechanical properties, deformation behaviour and relaxation of biopolymer chains and proteins have been the subject of much interest in recent years because of their importance in understanding the structure of cells and muscles.
Molecular modelling techniques are generally based on ab initio electronic structure calculations, semi-empirical methods or molecular mechanics. Molecular mechanics approaches do not take account of electron transfer processes, which can be crucially important, but instead rely on the use of parametrised interatomic force fields which are assumed to be transferable. Although electron reorganisation effects are not considered, these methods can be usefully applied to study the conformation and dynamics of large systems over long time scales.
We have developed and applied such methods to study protein folding, DNA translocation as well as studying molecular motor mechanisms. This is done by constructing minimalist models and determining the potential parameters before carrying out Monte-Carlo (MC) and molecular dynamics (MD) simulations. For example, in modelling DNA translocation through cell membrane pores (alpha-hemolysin) potential profiles are constructed (as in the figures below) and these were used in our MC and MD simulations to extract translocation times and so study their dependences on the DNA sequence and on other external factors.
- Matthai, C. C. and March, N. H. 2011. The application of condensed matter methods to the study of the conformation and elastic properties of biopolymers and the transport of DNA through cell membranes. Theoretical Chemistry Accounts 130 (4-6), pp.1155-1167. (10.1007/s00214-011-1022-9)
- March, N. H. and Matthai, C. C. 2009. The application of quantum chemistry and condensed matter theory in studying amino-acids, protein folding and anticancer drug technology. Theoretical Chemistry Accounts 125 (3-6), pp.193-201. (10.1007/s00214-009-0558-4)
- Matthai, C. C. and Loebl, H. C. 2004. Simulation Studies of Protein Translocation in Mitochondria. Physica A Statistical Mechanics and its Applications 342 (3-4), pp.612-622. (10.1016/j.physa.2004.05.039)
- Randel, R. , Loebl, H. C. and Matthai, C. C. 2004. Molecular dynamics simulations of polymer translocations. Macromolecular Theory and Simulations 13 (5), pp.387-391. (10.1002/mats.200300019)
- Loebl, H. C. et al., 2003. Simulation Studies of Polymer Translocation through a Channel. Physical Review E 67 (4), pp.04191301-04191305. (10.1103/PhysRevE.67.041913)