Improving molecular docking through eHiTS’ tunable scoring function

We present three complementary approaches for score-tuning that improve docking performance in pose prediction, virtual screening and binding affinity assessment. The methodology utilizes experimental data to customize the scoring function for the system of interest considering the specific docking scenario. The tuning approach, which has been implemented as an automated utility in eHiTS, is introduced as a solution to one of the conundrums of the molecular docking paradigm, namely, the lack of a universally well performing scoring function. The accuracy of scoring functions has been shown to be generally system-dependent, and particularly lacking for binding energy and bio-activity predictions. In the proposed approach, pose and energy predictions are enhanced by adjusting the relative weights of the eHiTS energy terms to improve score-RMSD or score-affinity correlations. In a virtual screening context ligand-based similarity is used to rescale the docking score such that better enrichment factors are achieved. We discuss the algorithmic details of the methods, and demonstrate the effects of score tuning on a variety of targets, including CDK2, BACE1 and neuraminidase, as well as on the popular benchmarks—the Directory of Useful Decoys and the PDBBind database.     

Piecewise adiabatic population transfer in a molecule via a wave packet

We propose a class of schemes for robust population transfer between quantum states that utilize trains of coherent pulses, thus forming a generalized adiabatic passage via a wave packet. We study piecewise stimulated Raman adiabatic passage with pulse-to-pulse amplitude variation, and piecewise chirped Raman passage with pulse-to-pulse phase variation, implemented with an optical frequency comb. In the context of production of ultracold ground-state molecules, we show that with almost no knowledge of the excited potential, robust high-efficiency transfer is possible.     

Scale-free human migration and the geography of social networks

The “gravitational law of social interaction”, by which the probability of a social link decreases inversely with the square of the geographic distance, has been recently documented. The source of this spatial property of social networks, however, is yet unknown. The formation of social links is related to human dynamics both on the day-to-day, typically small scale, level of mobility, and on larger scale migration (or reallocation) movements. In this study we analyze human migration patterns by investigating the migration of 46.8 million individuals across the US during 1995-2000. We find that the probability of migration decreases as a power law of the distance, with exponent −1. We show that this finding offers an explanation for the gravitational law of social interaction. Possible explanations and implications of the scale-free migration pattern are discussed.     

An Apparatus for Production of Isotopically and Spin-Enriched Hydrogen for Induced Polarization Studies

An apparatus for the production of hydrogen for hydrogenation-induced polarization studies was developed. The apparatus provides hydrogen gas from a solid source, thereby simplifying the requirement for siting of the apparatus. The produced hydrogen can be either isotopically enriched (with deuterium) or spin-enriched (with parahydrogen). These specialty gases were produced at small predetermined quantities and ambient pressure. The properties of the hydrogen mixtures were characterized by gas-phase nuclear magnetic resonance. The T ₁ of the hydrogen mixtures (3.7 ms) was not affected by para-enrichment. The line width of the hydrogen signal in the para-enriched mixture was 34% larger. The reaction of ethyl propiolate hydrogenation served to evaluate the performance in terms of the ability to create hyperpolarized states. In this reaction, a polarization of 11.2% was measured for protons. Consecutive alkene hydrogenations as well as hydrogenations of the catalyst ligand resulted in additional hyperpolarized signals which were systematically assigned.     

Collision-induced rovibrational energy transfer in small polyatomic molecules: the role of intramolecular perturbations

ABSTRACT

Various forms of time-resolved optical double-resonance spectroscopy facilitate rotationally resolved measurements of collision-induced intramolecular vibration-to-vibration (V–V) energy-transfer processes, which take a gas-phase polyatomic molecule from one distinct rovibrational energy level to another. Of longstanding mechanistic interest are questions concerning the extent to which such V–V energy transfer (ET) may be influenced by intramolecular perturbations – notably Fermi resonance (and other anharmonic mixing effects) and Coriolis coupling – within polyatomic molecular rovibrational manifolds of interest. It is evident that quantum-mechanical interference effects can arise, either inhibiting or enhancing the probability of collision-induced ET in perturbed rovibrational manifolds of certain small gas-phase polyatomic molecules, notably CO₂, D₂CO and C₂H₂. This article focuses on a blend of high-resolution rovibrational spectroscopy (characterising initial and final molecular levels and their intramolecular perturbations) and collision dynamics (with colliding molecules defined in terms of isolated-molecule spectroscopic basis states). It aims to offer fresh insights and to consider some apparent mechanistic anomalies (e.g. collision-induced quasi-continuous background effects in the 4ν_CH rovibrational manifold of C₂H₂). Various reported experiments and related theoretical treatments are critically re-examined, in order to pose and address mechanistic questions some of which still challenge detailed understanding.     

Milnor link invariants and quantum 3-manifold invariants

Let be the 3-manifold invariant of Le, Murakami and Ohtsuki. We show that , where denotes terms of degree , if M is a homology 3-sphere obtained from by surgery on an n-component Brunnian link whose Milnor -invariants of length vanish.?We prove a realization theorem which is a partial converse to the above theorem.?Using the Milnor filtration on links, we define a new bifiltration on the vector space with basis the set of oriented diffeomorphism classes of homology 3-spheres. This includes the Milnor level 2 filtration defined by Ohtsuki. We show that the Milnor level 2 and level 3 filtrations coincide after reindexing. Received: October 23, 1998.     

A short proof of the jordan decomposition theorem

We present a short proof of the Jordan Decomposition Theorem     

2‐Chloro‐4,6‐di­methoxy‐1,3,5‐triazine

The mol­ecules of 2‐chloro‐4,6‐di­methoxy‐1,3,5‐triazine, C₅H₆ClN₃O₂, lie on a crystallographic mirror plane. There is a close contact of 3.180 (3) Å between one of the methyl C atoms and the N atom of a neighboring mol­ecule. Differential scanning calorimetry measurements show that methyl rearrangement does not take place in the solid state, despite the close proximity of the methyl group to the N atom.