Computer Simulations of Molecular Recognition in Antibody- Protein Association

提出的主要理论方法是布朗动力学(BD)。布朗动力学模拟的基本思想是在蛋白质间作用力的影响下，根据布朗运动模拟两个相对运动的蛋白质的络合过程。力的起源通常是静电的，并且已经采用了诸如泊松-玻尔兹曼(PB)方法的连续介质方法。在大多数BD计算中，结合蛋白都是用简单的模型来描述的，虽然这已经产生了定性正确的结果，但很难预测绝对结合速率常数。此外，还只考虑了流体动力相互作用的简单模型。我们建议a)为底物/靶建立一个详细的残留物水平模型，b)在该方法中考虑更精确的水动力效应。人们越来越认识到，模拟将成为实验研究的有价值的伙伴，我们希望建立布朗动力学作为研究大分子缔合动力学的有用方法的有效性。

The principal theoretical methodology proposed here is Brownian dynamics (BD). The basic idea in Brownian dynamics simulations is to model the complexation of two proteins undergoing relative motion according to Brownian motion under the influence of interprotein forces. The forces are often electrostatic in origin and continuum approaches such as the Poisson-Boltzmann (PB) method have been employed. In most BD calculations, the associating proteins have been described by simple models and while this has yielded qualitatively correct results, it has been difficult to predict absolute association rate constants. Also, only simple models of hydrodynamic interactions have been considered. We propose here to a) develop a detailed residue-level model for substrate/target and b) incorporate more accurate hydrodynamic effects into the method. It is increasingly recognized that simulations would serve as a valuable companion to experimental investigations and we want to establish the validity of Brownian dynamics as a useful method for studying kinetics of macromolecular association.