Non-covalent π-π interactions are central to chemical and biological processes, yet the full understanding of their origin that would unite the simplicity of empirical approaches with the accuracy of quantum calculations is still missing. Here we employ a quantum-mechanical Hamiltonian model for van der Waals interactions, to demonstrate that intermolecular electron correlation in large supramo...

Many protein-protein docking protocols are based on a shotgun approach, in which thousands of independent random-start trajectories minimize the rigid-body degrees of freedom. Another strategy is enumerative sampling as used in ZDOCK. Here, we introduce an alternative strategy, ReplicaDock, using a small number of long trajectories of temperature replica exchange. We compare replica exchange sa...

Success in high-resolution protein-protein docking requires accurate modeling of side-chain conformations at the interface. Most current methods either leave side chains fixed in the conformations observed in the unbound protein structures or allow the side chains to sample a set of discrete rotamer conformations. Here we describe a rapid and efficient method for sampling off-rotamer side-chain...

The configuration-interaction CI method is applied to the calculation of the structures of a number of positron binding systems, including e+Be, e+Mg, e+Ca, and e+Sr. These calculations were carried out in orbital spaces containing about 200 electron and 200 positron orbitals up to =12. Despite the very large dimensions, the binding energy and annihilation rate converge slowly with , and the fi...

In 1997 we celebrated the 20th anniversary of the discovery of the b quark. What started out as a bump in the dimuon invariant mass spectrum has turned into the exciting field of heavy flavor physics. Weak decays of heavy quarks provide access to fundamental parameters of the Standard Model, in particular the weak mixing angles of the Cabibbo-Kobayashi-Maskawa matrix. There is great hope that e...

We present Fleksy, a new approach to consider both ligand and receptor flexibility in small molecule docking. Pivotal to our method is the use of a receptor ensemble to describe protein flexibility. To construct these ensembles, we use a backbone-dependent rotamer library and implement the concept of interaction sampling. The latter allows the evaluation of different orientations of ambivalent ...

A popular approach to the computational modeling of ligand/receptor interactions is to use an empirical free energy like model with adjustable parameters. Parameters are learned from one set of complexes, then used to predict another set. To improve these empirical methods requires an independent way to study their inherent errors. We introduce a toy model of ligand/receptor binding as a workbe...