In this paper, we give an integral approximation for the elliptic operators with anisotropic coecients on smooth manifold. Using the integral approximation, the elliptic equation is tranformed to an integral equation. The integral approximation preserves the symmetry and coercivity of the original elliptic operator. Based on these good properties, we prove the convergence between the solutions of the integral equation and the original elliptic equation.

Ligand-receptor binding and unbinding are fundamental biomolecular processes and particularly essential to drug efficacy. Environmental water fluctuations, however, impact the corresponding thermodynamics and kinetics and thereby challenge theoretical descriptions. Here, we devise a holistic, implicit-solvent, multi-method approach to predict the (un)binding kinetics for a generic ligand-pocket model. We use the variational implicit-solvent model (VISM) to calculate the solute-solvent interfacial structures and the corresponding free energies, and combine the VISM with the string method to obtain the minimum energy paths and transition states between the various metastable (“dry” and “wet”) hydration states. The resulting dry-wet transition rates are then used in a spatially-dependent multi-state continuous-time Markov chain Brownian dynamics simulations, and the related Fokker–Planck equation calculations, of the ligand stochastic motion, providing the mean first-passage times for binding and unbinding. We find the hydration transitions to significantly slow down the binding process, in semi-quantitative agreement with existing explicit-water simulations, but significantly accelerate the unbinding process. Moreover, our methods allow the characterization of non-equilibrium hydration states of pocket and ligand during the ligand movement, for which we find substantial memory and hysteresis effects for binding versus unbinding. Our study thus provides a significant step forward towards efficient, physics-based interpretation and predictions of the complex kinetics in realistic ligand-receptor systems.

In this paper, we analyze the stability of the fourth order Runge-Kutta method for integrating semi-discrete approximations of time-dependent partial differential equations. Our study focuses on linear problems and covers general semi-bounded spatial discretizations. A counter example is given to show that the classical four-stage fourth order Runge-Kutta method can not preserve the one-step strong stability, even though the ordinary differential equation system is energy-decaying. But with an energy argument, we show that the strong stability property holds in two steps under an appropriate time step constraint. Based on this fact, the stability extends to general well-posed linear systems. As an application, we utilize the results to examine the stability of the fourth order Runge-Kutta approximations of several specific method of lines schemes for hyperbolic problems, including the spectral Galerkin method and the discontinuous Galerkin method.

The immersed boundary method has evolved into one of the most useful computational methods in studying fluid structure interaction. On the other hand, the immersed boundary method is also known to suffer from a severe timestep stability restriction when using an explicit time discretization. In this paper, we propose several efficient semi-implicit schemes to remove this stiffness from the immersed boundary method for the two-dimensional Stokes flow. First, we obtain a novel unconditionally stable semi-implicit discretization for the immersed boundary problem. Using this unconditionally stable discretization as a building block, we derive several efficient semi-implicit schemes for the immersed boundary problem by applying the small scale decomposition to this unconditionally stable discretization. Our stability analysis and extensive numerical experiments show that our semi-implicit schemes offer much better stability property than the explicit scheme. Unlike other implicit or semi-implicit schemes proposed in the literature, our semi-implicit schemes can be solved explicitly in the spectral space. Thus the computational cost of our semi-implicit schemes is comparable to that of an explicit scheme, but with a much better stability property.

We propose efficient Eulerian methods for approximating the finite-time Lyapunov exponent (FTLE). The idea is to compute the related flow map using the Level Set Method and the Liouville equation. There are several advantages of the proposed approach. Unlike the usual Lagrangian-type computations, the resulting method requires the velocity field defined only at discrete locations. No interpolation of the velocity field is needed. Also, the method automatically stops a particle trajectory in the case when the ray hits the boundary of the computational domain. The computational complexity of the algorithm is <i>O</i>(<i>x</i>^(<i>d</i>+1)) with <i>d</i> the dimension of the physical space. Since there are the same number of mesh points in the <i>x</i><i>t</i> space, the computational complexity of the proposed Eulerian approach is optimal in the sense that each grid point is visited for only <i>O</i>(1) time. We also extend the algorithm to compute the FTLE