Computer Simulations of Molecular Recognition in Antibody- Protein Association

这里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根据蛋白质间力影响下的布朗运动来模拟两种蛋白质在相对运动下的络合作用。力的来源通常是静电，连续介质方法如泊松-玻尔兹曼（PB）方法已被采用。在大多数BD计算中，相关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，但很难预测绝对的关联速率常数。此外，只考虑了水动力相互作用的简单模型。我们在此建议：a)为底物/目标建立详细的残留水平模型；b)将更精确的水动力效应纳入该方法。人们越来越认识到模拟将作为实验研究的有价值的伴侣，我们希望建立布朗动力学作为研究大分子结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.