Related papers: Rapid calculation of side chain packing and free e…
Molecular dynamics is a powerful tool for studying the thermodynamics and kinetics of complex molecular events. However, these simulations can rarely sample the required time scales in practice. Transition path sampling overcomes this…
The processes by which protein sidechains reach equilibrium during a folding reaction are investigated using both lattice and all-atom simulations. We find that rates of sidechain relaxation exhibit a distribution over the protein…
Free energy calculation is critical in predictive tasks such as protein folding, docking and design. However, rigorous calculation of free energy change is prohibitively expensive in these practical applications. The minimum potential…
The motion involved in barrier crossing for protein folding are investigated in terms of the chain dynamics of the polymer backbone, completing the microscopic description of protein folding presented in the previous paper. Local reaction…
A microscopic theory of the free energy barriers and folding routes for minimally frustrated proteins is presented, greatly expanding on the presentation of the variational approach outlined previously [J. J. Portman, S. Takada, P. G.…
Computational protein design aims at constructing novel or improved functions on the structure of a given protein backbone and has important applications in the pharmaceutical and biotechnical industry. The underlying combinatorial…
The computational design of novel protein structures has the potential to impact numerous scientific disciplines greatly. Toward this goal, we introduce FoldFlow, a series of novel generative models of increasing modeling power based on the…
In this article the configurational space of two simple protein models consisting of polymers composed of a periodic sequence of four different kinds of monomers is studied as a function of temperature. In the protein models, hydrogen bond…
Predicting the change in binding free energy ($\Delta \Delta G$) is crucial for understanding and modulating protein-protein interactions, which are critical in drug design. Due to the scarcity of experimental $\Delta \Delta G$ data,…
We develop a simple but rigorous model of protein-protein association kinetics based on diffusional association on free energy landscapes obtained by sampling configurations within and surrounding the native complex binding funnels. Guided…
Protein collapse can be viewed as a dynamical phase transition, during which new scales and collective variables become excited while the old ones recede and fade away. This causes formidable computational bottle-necks in approaches that…
We consider a simplified model of protein folding, with binary degrees of freedom, whose equilibrium thermodynamics is exactly solvable. Based on this exact solution, the kinetics is studied in the framework of a local equilibrium approach,…
Calculating relative free energies is a topic of substantial interest and has many applications including solvation and binding free energies, which are used in computational drug discovery. However, there remain the challenges of accuracy,…
Nuclear magnetic relaxation is widely used to probe protein dynamics. For decades, most analyses of relaxation in proteins have relied successfully on the model-free approach, forgoing mechanistic descriptions of motions. Model-free types…
We introduce a powerful iterative algorithm to compute protein folding pathways, with realistic all-atom force fields. Using the path integral formalism, we explicitly derive a modified Langevin equation which samples directly the ensemble…
A central goal of protein-folding theory is to predict the stochastic dynamics of transition paths --- the rare trajectories that transit between the folded and unfolded ensembles --- using only thermodynamic information, such as a…
Due to the time-scale limitations of all-atom simulation of proteins, there has been substantial interest in coarse-grained approaches. Some methods, like "Resolution Exchange," [E. Lyman et al., Phys. Rev. Lett. 96, 028105 (2006)] can…
The massively parallel computation of absolute binding free energy with a well-equilibrated system (MP-CAFEE) has been developed [H. Fujitani, Y. Tanida, M. Ito, G. Jayachandran, C. D. Snow, M. R. Shirts, E. J. Sorin, and V. S. Pande, J.…
Accurately modeling protein 3D structure is essential for the design of functional proteins. An important sub-task of structure modeling is protein side-chain packing: predicting the conformation of side-chains (rotamers) given the…
We propose and justify a new approach for fast calculation of the electrostatic interaction energy of clusters of charged particles in constrained energy minimization in the framework of rigid protein-ligand docking. Our ``blind search''…