Related papers: Concurrent and Adaptive Extreme Scale Binding Free…
Accurate prediction of binding free energies is critical to streamlining the drug development and protein design process. With the advent of GPU acceleration, absolute alchemical methods, which simulate the removal of ligand electrostatics…
Molecular docking is a key computational tool utilized to predict the binding conformations of small molecules to protein targets, which is fundamental in the design of novel drugs. Despite recent advancements in geometric deep…
Adaptive therapy is a dynamic cancer treatment protocol that updates (or "adapts") treatment decisions in anticipation of evolving tumor dynamics. This broad term encompasses many possible dynamic treatment protocols of patient-specific…
Our ability to calculate rates of biochemical processes using molecular dynamics simulations is severely limited by the fact that the time scales for reactions, or changes in conformational state, scale exponentially with the relevant…
Predicting the efficacy of a drug for a given individual, using high-dimensional genomic measurements, is at the core of precision medicine. However, identifying features on which to base the predictions remains a challenge, especially when…
We conduct a theoretical study of various solution methods for the adaptive fractionation problem. The two messages of this paper are: (i) dynamic programming (DP) is a useful framework for adaptive radiation therapy, particularly adaptive…
Sampling from the equilibrium distribution has always been a major problem in molecular simulations due to the very high dimensionality of conformational space. Over several decades, many approaches have been used to overcome the problem.…
The discovery of novel drug target (DT) interactions is an important step in the drug development process. The majority of computer techniques for predicting DT interactions have focused on binary classification, with the goal of…
We utilize a multiscale modeling framework to study the effect of shape, size and ligand composition on the efficacy of binding of a ligand-coated-particle to a substrate functionalized with the target receptors. First, we show how…
Agent harnesses increasingly determine the performance of language-model systems by deciding how models call tools, receive feedback, verify intermediate states, store memory, and revise solutions. Yet current test-time scaling analyses…
In this paper, we present a robust adaptive model predictive control (MPC) scheme for linear systems subject to parametric uncertainty and additive disturbances. The proposed approach provides a computationally efficient formulation with…
In this paper, a methodology is proposed that enables to analyze the sensitivity of the outcome of a therapy to unavoidable high dispersion of the patient specific parameters on one hand and to the choice of the parameters that define the…
Model-based design of experiments (MBDOE) is essential for efficient parameter estimation in nonlinear dynamical systems. However, conventional adaptive MBDOE requires costly posterior inference and design optimization between each…
The molecular distributions obtained from canonical Monte Carlo simulations can be used to find an approximate interaction energy. This serves as the basis of a method for estimating the binding free energy for a ligand to a protein which…
Absolute binding free energy (ABFE) calculations offer a theoretically rigorous approach for predicting protein--ligand binding affinities without the scaffold constraints of relative binding free energy (RBFE) perturbations. However, broad…
As a necessary process in drug development, finding a drug compound that can selectively bind to a specific protein is highly challenging and costly. Drug-target affinity (DTA), which represents the strength of drug-target interaction…
Model Predictive Control (MPC) is a successful control methodology, which is applied to increasingly complex systems. However, real-time feasibility of MPC can be challenging for complex systems, certainly when an (extremely) large number…
In recent years dynamical modelling has been provided with a range of breakthrough methods to perform exact Bayesian inference. However it is often computationally unfeasible to apply exact statistical methodologies in the context of large…
A recent tight-binding scheme provides a method for extending the results of first principles calculations to regimes involving $10^2 - 10^3$ atoms in a unit cell. The method uses an analytic set of two-center, non-orthogonal tight-binding…
Reliable evaluation of protein structure predictions remains challenging, as metrics like pLDDT capture energetic stability but often miss subtle errors such as atomic clashes or conformational traps reflecting topological frustration…