Sampling in In Silico Biomolecular Studies: Single-Stage Experiments vs Multiscale Approaches

Nevena Ilieva, Jiaojiao Liu, Xubiao Peng, Jianfeng He, Antti Niemi, Peicho Petkov, Leandar Litov

Abstract: In silico studies of biological molecules face the problem of sampling quality due to the systems size (in atom numbers), the time scale of the investigated processes and the admissible computational time step. Advances in hardware alone are incapable of resolving this problem and the efforts are oriented towards sampling techniques enhancements, multilevel system representations and development of multistage and multiscale methods through synergistic protocols from complementary approaches. We combine a mean field approach with all atom molecular dynamics (MD), to develop a multistage algorithm that can model protein folding and dynamics over very long time periods with atomic-level precision. We compare the quality of conformation-space sampling for villin headpiece (PDB ID 2F4K) with a 125 \(\upmu \)s long folding simulation performed on the dedicated supercomputer ANTON.