Yesterday, I got my latest content update from the Biophysical journal for my keyword search for CHARMM. The first article that caught my eyes was a paper by Qiang Cui and co-workers, a paper titled A finite element framework for studying the mechanical response of macromolecules: Application to the gating of the mechanosensitive channel MscL. The paper looks at the gating pathways of mechanisensitive ion channels of large conductance (MscL) in two bacterial using Finite Element Method (FEM), a technique routinely used in engineering to solve complex elasticity and structural analysis problems (e.g. for modeling the structural integrity of airframes). Using such methods on biological systems is part of a new trend that tries to go beyond the nano/micro-second timescales that traditional molecular dynamics (MD) methods are limited to.
Qiang Cui, whom I have known for some time, is a CHARMM developer and has taken his interest in multiscale phenomena to new heights. This paper presents a framework for multiscale modeling, specifically for mechanosensitive channels (I wonder if more generalization is at all possible). If I had to pick a weakness in the paper it is that the system is very specific. That said, I think the current study is just a first pass at building more general methods for studying such systems at multiple length and time scales.
MS channels are interesting systems since the kinds of atomistic simulations traditionally used to study biological processes are not ideally suited to studying mechanical forces and multiple time scales. The simple models developed by Cui and co-workers include only the TM helices as elastic rods embedded in an elastic membrane . They find that even with such simple representations, the results are in fairly good agreement with existing data.
The FEM models are parameterized using standard molecular mechanics energy functions (using CHARMM and several implicit membrane models in CHARMM). The key is the interaction potentials between FEM components, which are represented as simple pairwise potentials. The FEM calculations themselves are done using ABAQUS
I won’t go into the details of the theory or the results. For me the most important aspect of the paper is using FEM to study a biological process. True multiscale modeling has not yet found its way into the arsenal of most scientists, but I suspect that with the developments that have been seen in the last couple of years, the day is not far that those of us interested in studying biological phenomena will have more than traditional atomistic MD simulations and quantum mechanics to rely on. Personally I think in a few years, those interested in studying protein structure and function will require a healthy training in multiscale modeling (quantum chemistry, molecular dynamics, coarse grained simulations, continuum dynamics), bioinformatics, and mathematical modeling.
Further Reading
CHARMM Development Project
Cui Group Homepage
Mechanosensitive channels at UIUC
Multiscale modeling at Utah
Technorati Tags: Mechanosensitive channels, Molecular Simulation, Molecular Dynamics, FEM, Multiscale Modeling, Large Scale Simulations, Protein Structure and Function
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