MD simulations in studies of protein–membrane interactions. Validation of the computational approach
Membrane processes are important for a normal function of living cells. Most of the features of a cell membrane are determined by a lipid bilayer, which presets complicated and heterogeneous association of molecules malleable for external agency. Also, it modulates function of membrane and membrane-active peptides and proteins. Therefore, studies of protein-membrane interactions represent an intriguing challenge in the field of structural biology. To get the overall picture of the action of membrane systems (including atomic details of interactions) employment of experimental methods only is often insufficient. Application of high-performance multiprocessor computational facilities permits investigation of different membrane systems using molecular modeling techniques.
Among them, molecular dynamics (MD) is one of the most powerful methods. MD simulations of explicit water–lipid systems are successfully carried out in the Laboratory for several years. As a result, a large set of model bilayers and micells differing in lipid composition have been elaborated. Such models are used to study different classes of membrane-active proteins and peptides (toxins, antimicrobial, Trojan and fusion peptides etc.).
In spite of obvious limitations of current MD time scale (~10−7÷10−8 sec), the results of membrane simulations are capable of giving a realistic picture of action of such systems. For instance, essential structural and dynamic characteristics of model membranes lie in a good correspondence with the experimental data. (see fig.1 / table 1).
Comparison of simulation and experimental results (fig. 2) permits validation of elaborated models and applied modeling approaches, which are currently used in our studies of new biologically relevant membrane peptides and proteins.
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