Performance of the Cell processor for biomolecular simulations

The new Cell processor represents a turning point for computing intensive applications. Here, I show that for molecular dynamics it is possible to reach an impressive sustained performance in excess of 30 Gflops with a peak of 45 Gflops for the non-bonded force calculations, over one order of magnitude faster than a single core standard processor

Multiscale modelling of liquids with molecular specificity

The separation between molecular and mesoscopic length and time scales poses a severe limit to molecular simulations of mesoscale phenomena. We describe a hybrid multiscale computational technique which address this problem by keeping the full molecular nature of the system where it is of interest and coarse-graining it elsewhere. This is made possible by coupling molecular dynamics with a mesoscopic description of realistic liquids based on Landau's fluctuating hydrodynamics. We show that our scheme correctly couples hydrodynamics and that fluctuations, at both the molecular and continuum levels, are thermodynamically consistent. Hybrid simulations of sound waves in bulk water and reflected by a lipid monolayer are presented as illustrations of the scheme

La riabilitazione termale nel 150° Anniversario dell'Unità d'Italia. Un testimonial d'eccezione: Giuseppe Garibaldi.

Nell’anno in cui si celebra il 150° Anniversario dell’Unità d’Italia, il riemergere di alcune lettere di Giuseppe Garibaldi - che fanno riferimento ad un periodo di cure termali effettuato presso le Terme della Ficoncella e di Traiano (vicino Civitavecchia, Roma) - ci ha dato lo spunto per questo lavoro che intende considerare i numerosi trattamenti effettuati presso diverse stazioni termali italiane dall’Eroe dei Due Mondi per una patologia reumatica (probabilmente una poliartrite reumatoide) e per gli esiti di varie ferite di guerra, in particolare la ben nota ferita da arma da fuoco subita a livello dell’arto inferiore destro nel corso della battaglia d’Aspromonte, nel 1862

The impact of accelerator processors for high-throughput molecular modeling and simulation

Accepted versio

Determination of the chemical potential using energy-biased sampling

An energy-biased method to evaluate ensemble averages requiring test-particle insertion is presented. The method is based on biasing the sampling within the subdomains of the test-particle configurational space with energies smaller than a given value freely assigned. These energy-wells are located via unbiased random insertion over the whole configurational space and are sampled using the so called Hit&Run algorithm, which uniformly samples compact regions of any shape immersed in a space of arbitrary dimensions. Because the bias is defined in terms of the energy landscape it can be exactly corrected to obtain the unbiased distribution. The test-particle energy distribution is then combined with the Bennett relation for the evaluation of the chemical potential. We apply this protocol to a system with relatively small probability of low-energy test-particle insertion, liquid argon at high density and low temperature, and show that the energy-biased Bennett method is around five times more efficient than the standard Bennett method. A similar performance gain is observed in the reconstruction of the energy distribution.Comment: 10 pages, 4 figure

Kinetic characterization of the critical step in HIV-1 protease maturation

HIV maturation requires multiple cleavage of long polyprotein chains into functional proteins that include the viral protease itself. Initial cleavage by the protease dimer occurs from within these precursors, and yet only a single protease monomer is embedded in each polyprotein chain. Self-activation has been proposed to start from a partially dimerized protease formed from monomers of different chains binding its own N termini by self-association to the active site, but a complete structural understanding of this critical step in HIV maturation is missing. Here, we captured the critical self-association of immature HIV-1 protease to its extended amino-terminal recognition motif using large-scale molecular dynamics simulations, thus confirming the postulated intramolecular mechanism in atomic detail. We show that self-association to a catalytically viable state requires structural cooperativity of the flexible β-hairpin “flap” regions of the enzyme and that the major transition pathway is first via self-association in the semiopen/open enzyme states, followed by enzyme conformational transition into a catalytically viable closed state. Furthermore, partial N-terminal threading can play a role in self-association, whereas wide opening of the flaps in concert with self-association is not observed. We estimate the association rate constant (k(on)) to be on the order of ∼1 × 10(4) s(−1), suggesting that N-terminal self-association is not the rate-limiting step in the process. The shown mechanism also provides an interesting example of molecular conformational transitions along the association pathway