|
PresentationsRecent Advances in Coarse-Grained Simulations of Biomolecular SystemsShenzhen MSU-BIT University, Shenzhen, China Computational modeling of proteins and other biomolecules has become one of the key tools of modern biophysics, enabling detailed insight into intermolecular interactions and dynamical processes in biological systems. The need to model phenomena occurring over large temporal and spatial scales has driven the development of coarse-grained (CG) approaches, in which groups of atoms are replaced by effective interaction sites (“beads”). Such models substantially reduce computational costs compared to all-atom simulations and enable accelerated exploration of configurational space through simplified interaction potentials. This makes it possible to systematically investigate complex phenomena spanning a wide range of timescales, including membrane and membrane-protein dynamics, protein–protein and protein–ligand interactions, and conformational rearrangements in protein complexes. In this report, we review recent methodological advances as well as selected applications of coarse-grained modeling to topical problems in structural biology and biophysics. In particular, the use of CG approaches at early stages of drug discovery is discussed, including the identification of orthosteric, allosteric, and protein–protein interaction (PPI) binding sites, estimation of small-molecule permeability across biological barriers, and assessment of ligand affinity for molecular targets. In the field of protein-complex modeling, examples are presented demonstrating the successful application of coarse-grained methods to analyze mechanical properties under load, including multiscale simulations of the asymmetric detachment of the NDC80 complex from microtubules under directional force. Coarse-grained approaches are also shown to enable efficient exploration of configurational space for large protein assemblies containing intrinsically disordered regions, such as ion channels and even entire viral particles. Finally, in the context of membrane biophysics, we demonstrate the capabilities of coarse-grained modeling for studying interactions of amphiphilic maleic acid copolymers (SMA and related compounds) with lipid bilayers, which are used to extract membrane proteins and lipids into stable discoidal particles (SMALPs). Applications relevant to public health are also discussed, including studies of interactions between widely used cationic antiseptics and bacterial membranes, as well as investigations of the dynamics of the SARS-CoV-2 envelope (E) protein and the effects of its post-translational modifications on the protein’s ability to induce and sense membrane curvature, potentially linked to oligomer assembly and viral particle formation.
|
