Developing and applying new theoretical and computational methods to study complex condensed phase systems
Material for Download
Multi-scale Coarse-graining (MS-CG) Force Matching (FM) code is now publicly available for download
Reproducibility in the coarse-grained model is essential, especially when vital information below the CG resolution is lost during the CG process. In the case of a two-site methanol molecule, this problem becomes apparent since the hydrogen-bonding topology (either donor or acceptor) among -OH beads is lost, resulting in inaccurate local structures. To surmount this challenge, we apply the Ultra-Coarse-Grained (UCG) theory to construct a high-fidelity CG model with implicit hydrogen-bonding. Since hydrogen bonding is a local phenomenon, the internal states of the hydrogen-bonding participating CG sites are determined by the local density of the CG sites. This strategy is then applied to two different hydrogen bonding motifs: chain-like and ring-like. For both motifs including amino acid building blocks, the UCG models show better structural correlations (pair, triplet, and local number density) compared to the conventional MS-CG models. These results strongly suggest that the UCG theory can significantly improve the reproducibility of the CG model in the complex condensed system.
In this work, we built up the first rigorous bridge between atomistic and supramolecular mesoscopic models of fluids. A delicate dynamic coarse-graining mapping scheme, whose idea originates from the centroidal Voronoi tesellation algorithm in computational geometry, was designed to account for the microscopic momentum transport that governs the fluid motion at mesoscale. Besides, a systematic parameterization method based on Mori-Zwanzig formalism was developed and faithfully reproduces the statistical and dynamical characteristics of the coarse-grained trajectory. The new dynamical coarse-grained mapping scheme and the parameterization protocol open up an avenue for direct bottom-up construction of mesoscopic models of complex fluids in a Lagrangian description.
Molecular transport through membranes: Accurate permeability coefficients from multidimensional potentials of mean force and local diffusion constants
Estimating the permeability coefficient of small molecules through lipid bilayer membranes plays an essential role in the development of effective drug candidates. However, the absolute permeability coefficients obtained from pre-existing computer simulation methods are usually off by orders of magnitude, mostly due to the poor convergence of permeation free energy profiles and over-simplified diffusion models. To overcome these obstacles, we describe the permeation process using multiple reaction coordinates and estimate the permeability along the minimum free energy path of the multidimensional potential of mean force. A combination of cutting-edge metadynamics enhanced sampling techniques, and improved representation of the permeation process leads to a considerably more accurate estimation of permeability coefficients compared to pre-existing methods.
For influenza virus to release from the infected host cell, controlled viral budding must finalize with membrane scission of the viral envelope. Curiously, influenza carries its own protein, M2, which can sever the membrane of the constricted budding neck. Here we elucidate the physical mechanism of clustering and spatial localization of the M2 scission proteins through a combined computational and experimental approach.
Hydrolysis of the nucleotide bound to each subunit of actin serves as an important clock that governs the remodeling of the cytoskeletal network. Whether the hydrolysis and the subsequent phosphate release act independently or are somehow coupled across different subunits in the filament network has been debated for over three decades. Here, we developed a systematic multi-scale modeling framework by combining atomistic simulations, the Ultra-Coarse-Graining approach, and Markov State Modeling, that addresses this issue.
In this work, we have demonstrated the application of the recently developed Ultra-CG (UCG) theory to heterogeneous systems: liquid/vapor and liquid/liquid interfaces. Due to the inhomogeneous nature of an interfacial system, the conventional MS-CG framework fails to capture the structure and directionality of molecules, resulting in the breakdown of the interfacial density profile. In order to resolve the limitation of the MS-CG method, we have designed the UCG framework to systematically distinguish different local environments in interfacial systems and faithfully recapitulates structural correlations in the interfacial systems. More fascinatingly, the CG interactions obtained by the UCG methodology are transferable to corresponding bulk states. This transferability was observed in both liquid/vapor and liquid/liquid systems: the UCG methodology can impart transferable CG models while retaining high accuracy.
In this work, we studied the interactions between actin and the FH2 domains of formins Cdc12, Bni1 and mDia1 to understand the factors underlying their different rates of polymerization.