Michael D. Altman

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Computer simulation is an important tool for improving our understanding of biomolecule electrostatics, in part to aid in drug design. However, the numerical techniques used in these simulation tools do not exploit fast solver approaches widely used in analyzing integrated circuit interconnects. In this paper we describe one popular formulation used to(More)
—This paper presents a fast boundary-element method (BEM) algorithm that is well suited for solving electrostatics problems that arise in traditional and bio-microelectromecha-nical systems (bio-MEMS) design. The algorithm, FFTSVD, is Green's-function-independent for low-frequency kernels and efficient for inhomogeneous problems. FFTSVD is a multiscale(More)
We present a boundary-element method (BEM) implementation for accurately solving problems in biomolecular electrostatics using the linearized Poisson-Boltzmann equation. Motivating this implementation is the desire to create a solver capable of precisely describing the geometries and topologies prevalent in continuum models of biological molecules. This(More)
Surface formulations of biophysical modeling problems offer attractive theoretical and computational properties. Numerical simulations based on these formulations usually begin with discretization of the surface under consideration; often, the surface is curved, possessing complicated structure and possibly singularities. Numerical simulations commonly are(More)
We explore the applicability of an additive treatment of substituent effects to the analysis and design of HIV protease inhibitors. Affinity data for a set of inhibitors with a common chemical framework were analyzed to provide estimates of the free energy contribution of each chemical substituent. These estimates were then used to design new inhibitors(More)
The rapid evolution of HIV under selective drug pressure has led to multidrug resistant (MDR) strains that evade standard therapies. We designed highly potent HIV-1 protease inhibitors (PIs) using the substrate envelope model, which confines inhibitors within the consensus volume of natural substrates, providing inhibitors less susceptible to resistance(More)
The Problem: Biomolecular structure and interactions in an aqueous environment are determined by a complicated interplay between physical and chemical forces including solvation, electrostatics, van der Waals forces, the hydrophobic effect, and covalent bonding. Electrostatic forces have received a great deal of study due to their long-range nature and the(More)
Acquired resistance to therapeutic agents is a significant barrier to the development of clinically effective treatments for diseases in which evolution occurs on clinical time scales, frequently arising from target mutations. We previously reported a general strategy to design effective inhibitors for rapidly mutating enzyme targets, which we demonstrated(More)
— We present a PDE-constrained approach to optimizing the electrostatic interactions between two biomolecules. These interactions play important roles in the determination of binding affinity and specificity, and are therefore of significant interest when designing a ligand molecule to bind tightly to a receptor. Using a popular continuum model and(More)