标题： 通过鲁棒自由能推断比较采样方法：应用于钙调蛋白 显示英文标题

标题： Comparison of Sampling Methods via Robust Free Energy Inference: Application to Calmodulin

摘要： 基于贝叶斯推断的自由能景观估计方法被提出并用于比较热增强采样方法与常规分子动力学在效率上的差异，其中模拟是在钙调蛋白的两个结合状态上进行的。 所提出的自由能估计方法（GM方法）与其他估计器进行了比较，使用一个玩具模型表明GM方法提供了不受过拟合影响的稳健估计。 GM方法的连续性以及对基函数数量的预测推断，在稀疏数据上提供了更好的估计。 我们发现自由能扩散特性决定了采样方法的有效性，因此扩散占主导的无配体钙调蛋白最有效地由常规分子动力学采样，而具有崎岖自由能景观的全配体则由增强方法更好地采样。 显示英文摘要

摘要： A free energy landscape estimation-method based on Bayesian inference is presented and used for comparing the efficiency of thermally enhanced sampling methods with respect to regular molecular dynamics, where the simulations are carried out on two binding states of calmodulin. The proposed free energy estimation method (the GM method) is compared to other estimators using a toy model showing that the GM method provides a robust estimate not subject to overfitting. The continuous nature of the GM method, as well as predictive inference on the number of basis functions, provide better estimates on sparse data. We find that the free energy diffusion proper- ties determine sampling method effectiveness, such that the diffusion dominated apo-calmodulin is most efficiently sampled by regular molecular dynamics, while the holo with its rugged free energy landscape is better sampled by enhanced methods.