Variational Methods for Biomolecular Modeling

Structure, function and dynamics of many biomolecular systems can be characterized by the energetic variational principle and the corresponding systems of partial differential equations (PDEs). This principle allows us to focus on the identification of essential energetic components, the optimal parametrization of energies, and the efficient computational implementation of energy variation or minimization. Given the fact that complex biomolecular systems are structurally non-uniform and their interactions occur through contact interfaces, their free energies are associated with various interfaces as well, such as solute-solvent interface, molecular binding interface, lipid domain interface, and membrane surfaces. This fact motivates the inclusion of interface geometry, particular its curvatures, to the parametrization of free energies. Applications of such interface geometry based energetic variational principles are illustrated through three concrete topics: the multiscale modeling of biomolecular electrostatics and solvation that includes the curvature energy of the molecular surface, the formation of microdomains on lipid membrane due to the geometric and molecular mechanics at the lipid interface, and the mean curvature driven protein localization on membrane surfaces. By further implicitly representing the interface using a phase field function over the entire domain, one can simulate the dynamics of the interface and the corresponding energy variation by evolving the phase field function, achieving significant reduction of the number of degrees of freedom and computational complexity. Strategies for improving the efficiency of computational implementations and for extending applications to coarse-graining or multiscale molecular simulations are outlined.Comment: 36 page

Implicit Total Variation Diminishing (TVD) schemes for steady-state calculations

The application of a new implicit unconditionally stable high resolution total variation diminishing (TVD) scheme to steady state calculations. It is a member of a one parameter family of explicit and implicit second order accurate schemes developed by Harten for the computation of weak solutions of hyperbolic conservation laws. This scheme is guaranteed not to generate spurious oscillations for a nonlinear scalar equation and a constant coefficient system. Numerical experiments show that this scheme not only has a rapid convergence rate, but also generates a highly resolved approximation to the steady state solution. A detailed implementation of the implicit scheme for the one and two dimensional compressible inviscid equations of gas dynamics is presented. Some numerical computations of one and two dimensional fluid flows containing shocks demonstrate the efficiency and accuracy of this new scheme

The diffuse Nitsche method: Dirichlet constraints on phase-field boundaries

We explore diffuse formulations of Nitsche's method for consistently imposing Dirichlet boundary conditions on phase-field approximations of sharp domains. Leveraging the properties of the phase-field gradient, we derive the variational formulation of the diffuse Nitsche method by transferring all integrals associated with the Dirichlet boundary from a geometrically sharp surface format in the standard Nitsche method to a geometrically diffuse volumetric format. We also derive conditions for the stability of the discrete system and formulate a diffuse local eigenvalue problem, from which the stabilization parameter can be estimated automatically in each element. We advertise metastable phase-field solutions of the Allen-Cahn problem for transferring complex imaging data into diffuse geometric models. In particular, we discuss the use of mixed meshes, that is, an adaptively refined mesh for the phase-field in the diffuse boundary region and a uniform mesh for the representation of the physics-based solution fields. We illustrate accuracy and convergence properties of the diffuse Nitsche method and demonstrate its advantages over diffuse penalty-type methods. In the context of imaging based analysis, we show that the diffuse Nitsche method achieves the same accuracy as the standard Nitsche method with sharp surfaces, if the inherent length scales, i.e., the interface width of the phase-field, the voxel spacing and the mesh size, are properly related. We demonstrate the flexibility of the new method by analyzing stresses in a human vertebral body

Method of lines transpose: High order L-stable O(N) schemes for parabolic equations using successive convolution

We present a new solver for nonlinear parabolic problems that is L-stable and achieves high order accuracy in space and time. The solver is built by first constructing a single-dimensional heat equation solver that uses fast O(N) convolution. This fundamental solver has arbitrary order of accuracy in space, and is based on the use of the Green's function to invert a modified Helmholtz equation. Higher orders of accuracy in time are then constructed through a novel technique known as successive convolution (or resolvent expansions). These resolvent expansions facilitate our proofs of stability and convergence, and permit us to construct schemes that have provable stiff decay. The multi-dimensional solver is built by repeated application of dimensionally split independent fundamental solvers. Finally, we solve nonlinear parabolic problems by using the integrating factor method, where we apply the basic scheme to invert linear terms (that look like a heat equation), and make use of Hermite-Birkhoff interpolants to integrate the remaining nonlinear terms. Our solver is applied to several linear and nonlinear equations including heat, Allen-Cahn, and the Fitzhugh-Nagumo system of equations in one and two dimensions