Distributed automated docking of flexible ligands to proteins: Parallel applications of AutoDock 2.4

Summary AutoDock 2.4 predicts the bound conformations of a small, flexible ligand to a nonflexible macromolecular target of known structure. The technique combines simulated annealing for conformation searching with a rapid grid-based method of energy evaluation based on the AMBER force field. AutoDock has been optimized in performance without sacrificing accuracy; it incorporates many enhancements and additions, including an intuitive interface. We have developed a set of tools for launching and analyzing many independent docking jobs in parallel on a heterogeneous network of UNIX-based workstations. This paper describes the current release, and the results of a suite of diverse test systems. We also present the results of a systematic investigation into the effects of varying simulated-annealing parameters on molecular docking. We show that even for ligands with a large number of degrees of freedom, root-mean-square deviations of less than 1 Å from the crystallographic conformation are obtained for the lowest-energy dockings, although fewer dockings find the crystallographic conformation when there are more degrees of freedom.The AutoDock 2.4 suite is written in ANSI C, and is supplied with Makefiles for the following platforms: Convex, DEC Alpha OSF/1, Hewlett-Packard Precision Architecture, Silicon Graphics, and Sun. The AutoDock suite of programs is freely available to the noncommercial scientific community and to educational establishments. Further information, including additional figures and MPEG animations showing all docked conformations for each test system, can be found at the following URL: http://www.scripps.edu/pub/olson-web/doc/autodock.     

Balancing families of sets

Given k finite sets S₁,…,S_k, to what extent is it possible to partition their union into two parts A and B in such a way that, for each j, S_j ∩ A and S_j ∩ B contain approximately the same number of elements? Bounds are found for this and similar questions.     

Step structures on III-V phosphide (001) surfaces: how do steps and Sb affect CuPt ordering of GaInP2?

The observation of III-V phosphide (001)-(2 x 2) surfaces makes it possible to solve a long standing mystery of step structures. First-principles calculations show that a bulklike type-B step on a hydrogenated 2 x 2 surface is more stable than a rebonded one by 1.1 eV/unit step. In contrast, this energy difference for a H-free beta(2 x 4) surface is only 0.5 eV/unit step. The large difference explains why the CuPt ordering of GaInP is stronger in metal-organic chemical vapor deposition than in molecular beam epitaxy. However, a minute amount of Sb will preferentially attach to the 2 x 2 surface steps and induce additional step structures that cause ordering disruption.     

Nonoccupational noise: exposures associated with routine activities

Efforts to characterize nonoccupational noise exposures have focused primarily on infrequent, episodic events. Few studies have assessed noise levels resulting from routine daily activities. In the current study, 112 construction workers wore datalogging noise dosimeters and simultaneously completed activity logs during two phases of data collection. The 81 subjects monitored in phase 1 received logs listing numerous preselected occupational and nonoccupational activities, while the 31 subjects monitored in phase 2 used free-field logs and reported nonoccupational activities in greater detail. Nearly all of the 221,439 1-min intervals of nonoccupational L(eq) level and activity reporting were below 70 dBA; only a small percentage exceeded 80 dBA. The primary contributor to nonoccupational noise exposure was traveling in a car or bus, while time at home contributed the least. One hundred seventy 24-h L(eq) levels were computed from the 1-min noise level data. The percentage of phase 2 workday L(eq(24)) levels which exceeded 80 dBA was higher than that of the nonworkday levels. The mean L(eq(24)) level of phase 2 workdays was higher than that of nonworkdays, and the difference was statistically significant. Routine nonoccupational noise exposures contributed much less to total noise dose than occupational exposures in the subjects evaluated.     

A nonmusical paradigm for identifying absolute pitch possessors

The ability to identify and reproduce sounds of specific frequencies is remarkable and uncommon. The etiology and defining characteristics of this skill, absolute pitch (AP), have been very controversial. One theory suggests that AP requires a specific type of early musical training and that the ability to encode and remember tones depends on these learned musical associations. An alternate theory argues that AP may be strongly dependent on hereditary factors and relatively independent of musical experience. To date, it has been difficult to test these hypotheses because all previous paradigms for identifying AP have required subjects to employ knowledge of musical nomenclature. As such, these tests are insensitive to the possibility of discovering AP in either nonmusicians or musicians of non-Western training. Based on previous literature in pitch memory, a paradigm is presented that is intended to distinguish between AP possessors and nonpossessors independent of the subjects' musical experience. The efficacy of this method is then tested with 20 classically defined AP possessors and 22 nonpossessors. Data from these groups strongly support the validity of the paradigm. The use of a nonmusical paradigm to identify AP may facilitate research into many aspects of this phenomenon.     

Optical characterization of a nanoscale incommensurate pitch in a new liquid-crystal phase

As a remarkable orientationally ordered soft-condensed matter system, the smectic-C*(alpha) phase exhibits an incommensurate nanoscale helical pitch of more than four smectic layers. Recent theoretical advances predict the existence of a new phase showing a helical pitch of less than four smectic layers (<16 nm). By applying a novel optical technique to the study of freestanding films with increments in thickness of one smectic layer, we have measured the size of this pitch using 633 nm HeNe laser light. Our results confirm the existence of the newly predicted phase in one unique compound.     

ITQ-12: a new microporous silica polymorph potentially useful for light hydrocarbon separations

The new synthetic form of microporous crystalline silica, denoted as ITQ-12, shows a high potential for the separation of propane and propene from its mixtures.     

Intracochlear pressure measurements related to cochlear tuning

Pressure in turn one of the scala tympani (s.t.) was measured close to the basilar membrane (b.m.) and at additional positions as the pressure sensor approached and/or withdrew from the b.m. The s.t. pressure measured within about 100 microm of the b.m. varied rapidly in space at frequencies around the region's best frequency. Very close to the b.m. the s.t. pressure was tuned and scaled nonlinearly with sound level. The scala vestibuli (s.v.) pressure was measured at one position close to the stapes within seconds of the s.t. pressure and served primarily as a reference pressure. The driving pressure across the organ of Corti and the b.m. velocity were derived from the pressure data. Both were tuned and nonlinear. Therefore, their ratio, the specific acoustic impedance of the organ of Corti complex, was relatively untuned, and only subtly nonlinear. The impedance was inspected specifically for negative resistance (amplification) and resonance. Both were detected in some instances; taken as a whole, the current results constrain the possibilities for these qualities.     

Moving Wigner glasses and smectics: dynamics of disordered Wigner crystals

We examine the dynamics of driven classical Wigner solids interacting with quenched disorder from charged impurities. For strong disorder, the initial motion is plastic, in the form of crossing winding channels. For increasing drive, there is a reordering into a moving Wigner smectic with the electrons moving in separate 1D channels. These different dynamic phases can be related to the conduction noise and I(V) curves. For strong disorder, we show criticality in the voltage onset just above depinning. We obtain the dynamic phase diagram for driven Wigner solids and demonstrate a finite threshold of force for transverse sliding, recently observed experimentally.