A Novel Computational Method for Diffuse Interface Models of Implicit Solvation of Biomolecules

在过去的二十年里，隐式溶剂模型是非常重要的生物分子建模社区与成千上万的示例性应用在文献中，由于其低计算成本和相对较高的精度。隐式溶剂模型的准确性依赖于溶质-溶剂界面的几何描述和在分子附近定义的溶剂介电分布。成功地实现了本项目中所提出的模型，并真实地生成了溶质-溶剂光滑边界，这将大大提高这些隐式溶剂模型的准确性和效率。这项调查将直接集成到现有的隐式溶剂软件和可视化软件包，以确保广泛的用途，由一个既定的用户社区的研究人员在化学，物理学和生物学。此外，所提出的工作将提出一个非传统的计算方法，扩散界面模型应用于空间多尺度建模在数学生物学。成功的发展所提出的工作将成为一个有价值的computationaltool研究离散和连续模型所描述的区域之间的过渡。该结果将对广泛的科学领域产生潜在影响，例如癌症研究和药物设计中的多尺度建模。本计画的目标是发展一种新的计算方法来模拟生物分子的显式溶剂化扩散界面模型。计算方法将是数学上严格和计算效率，以产生物理上现实的溶质-溶剂光滑边界的自由能最小化。为此，本文提出了一种新的构造方法，将有界容许函数的变分问题转化为等价的无约束问题，从而可以直接应用传统的Euler-Lagrange方程。这一新的计算公式将采用先进的计算算法来实现，以确保其准确性，稳定性和效率，并将通过几个常见的生物分子建模任务进行验证。该奖项反映了NSF的法定使命，并被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

In the past two decades, implicit solvent models are of tremendous importance to the biomolecularmodeling community with thousands of exemplary applications in the literature due to their lowcomputational cost and relatively high accuracy. The accuracy of implicit solvent models dependson the geometric description of the solute-solvent interface and the solvent dielectric profile thatis defined near the molecules. Successful implementations of the proposed model in this project withrealistically generated solute-solvent smooth boundaries will greatly improve the accuracy andefficiency of these implicit solvent models. This investigation will be directly integrated into existingimplicit solvent software and visualization packages to ensure extensive usages by an establisheduser community of researchers in chemistry, physics, and biology. Moreover, the proposed work will present an unconventional computational method for diffuse interface models applied to spatial multiscale modeling in mathematical biology. Successful development of the proposed work will become a valuable computationaltool for studying the transition between regions described by discrete and continuum models. The outcome will have potential impacts across a wide range of scientific fields such as multiscalemodeling in cancer research and drug design. The goal of this project is to develop a novel computational method for diffuse interface models ofimplicit solvation of biomolecules. The computational approach will be mathematically rigorous andcomputationally efficient to generate physically realistic solute-solvent smooth boundaries by freeenergy minimization. To this end, an innovative construction is proposed to transform a variationalproblem subject to bounded admissible functions into an equivalent unconstrained problem sothat the traditional Euler-Lagrange Equation can be applied directly. This new computationalformulation will be implemented with advanced computational algorithms to ensure their accuracy,stability, and efficiency, and it will be validated by several common biomolecular modeling tasks.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.