Holographic multiscale method used with non-biased atomistic forcefields for simulation of large transformations in protein

Abstract

Abstract.We present a multiscale approach for simulating protein flexibility. The originality of our method is its ability to perform dynamic multiscaling based on continuous revaluation of overlapping areas. The holographic multiscale method overcomes the limitations of motions determined by predefined and fixed high-level descriptions and allows the reproduction of residue-specific impact on large scale motion. The method is tested with two different nonbiased all atom implicit solvent forcefields. These show stretched proteins A and G, with maintained secondary structure, folding back near native states in a small number of transition events, demonstrating the advantages of this multiscale approach.

The Activation-Relaxation Technique: ART Nouveau and Kinetic ART

“…In protein A, ART nouveau managed to identify metastable ordered structures of higher energy that can shed light on close homological sequences. Finally, ART nouveau is also a very interesting tool for exploring conformation of large biological systems, if it is coupled with internal coordinates and multiscale representations [73,74].…”

A Local Rigid Body Framework for Global Optimization of Biomolecules

“…Significant effort has also been directed towards multiscale modelling, where various parts of the computational domain are represented at different resolution, [8][9][10] or where large-scale cooperative motion is first explored, followed by relaxation at an atomistic level. 11,12 We describe here a local rigid body framework, where arbitrary sets of atoms may be grouped as rigid bodies. This procedure reduces the number of degrees of freedom during simulations or geometry optimization, thus providing a significant gain in computational efficiency.…”

“…Coarse-graining − allows us to achieve longer length and time scales by integrating out less relevant microscopic details. Significant effort has also been directed toward multiscale modeling, where various parts of the computational domain are represented at different resolutions, − or where large-scale cooperative motion is first explored, followed by relaxation at an atomistic level. , …”