Optimization Algorithms for Chemoinformatics and Material-informatics

Modeling complex phenomena in chemoinformatics and material-informatics can often be formulated as single-objective or multi-objective optimization problems (SOOPs or MOOPs). For example, the design of new drugs or new materials is inherently a MOOP since drugs/materials require the simultaneous optimization of multiple parameters

Method for Computing Protein Binding Affinity

A Monte Carlo method is given to compute the binding affinity of a ligand to a protein. The method involves extending configuration space by a discrete variable indicating whether the ligand is bound to the protein and a special Monte Carlo move which allows transitions between the unbound and bound states. Provided that an accurate protein structure is given, that the protein-ligand binding site is known, and that an accurate chemical force field together with a continuum solvation model is used, this method provides a quantitative estimate of the free energy of binding.Comment: RevTex, 10 pages with 5 figures. Explanatory figure adde

THE MANY DIFFERENT ROLES OF MOLECULAR DYNAMICS IN DRUG DISCOVERY

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Determinação dos teores de mercúrio em solos, sedimentos e águas fluviais em área de mineração de ouro: estudo de caso do município de Paracatu (MG)

O mercúrio é um contaminante de elevada toxicidade à saúde humana e à biota, o que tem despertado o interesse pelo entendimento de seu comportamento no ambiente. O presente trabalho trata da avaliação dos teores de mercúrio em águas, sedimentos fluviais e solos oriundos de uma área influenciada por mineração de ouro (Paracatu, MG). Para tanto, a campanha de coleta foi realizada em Setembro/2010. A caracterização físico-química das águas, realizada em campo, foi baseada na determinação do pH, condutividade elétrica, sólidos dissolvidos, temperatura e oxigênio dissolvido. A caracterização mineralógica dos solos e sedimentos foi realizada através de difratometria de raios-X. A quantificação dos teores de mercúrio foi efetuada utilizando o equipamento LUMEX, e em distintas frações granulométricas dos solos e sedimentos. Índices de poluição (IGEO e IGDG) foram calculados de forma a avaliar o comportamento e a intensidade da contaminação. Os resultados revelaram baixas concentrações de mercúrio para as amostras de água, porém anomalias na condutividade elétrica e no oxigênio dissolvido em relação à legislação brasileira. Os valores de pH dos solos e sedimentos ficaram na faixa da neutralidade. A caracterização mineralógica indicou a ocorrência de fases minerais comuns a ambientes que sofreram intenso intemperismo, tais como caulinita, gibbsita e hematita. As concentrações de mercúrio nos sedimentos e solos demonstraram a ocorrência de hot-spots de contaminação para as áreas diretamente influenciadas pela mineração de ouro, bem como nas áreas situadas próximas a despejo de esgoto doméstico, sugerindo com isso que o mercúrio pode ser utilizado como indicador de degradação ambiental oriunda da mineração (apresentando valores acima daqueles propostos pela Resolução do CONAMA 420). Portanto, com relação à contaminação por mercúrio, no presente, não é possível afirmar que exista impacto direto da mineração de ouro nas anomalias detectadas na região, já que essas são oriundas de rejeitos domésticos. Assim, a área não estando impactada por mercúrio decorrente da atividade mineradora

A process evaluation of the scale up of a youth-friendly health services initiative in northern Tanzania

BACKGROUND: While there are a number of examples of successful small-scale, youth-friendly services interventions aimed at improving reproductive health service provision for young people, these projects are often short term and have low coverage. In order to have a significant, long-term impact, these initiatives must be implemented over a sustained period and on a large scale. We conducted a process evaluation of the 10-fold scale up of an evaluated youth-friendly services intervention in Mwanza Region, Tanzania, in order to identify key facilitating and inhibitory factors from both user and provider perspectives. METHODS: The intervention was scaled up in two training rounds lasting six and 10 months. This process was evaluated through the triangulation of multiple methods: (i) a simulated patient study; (ii) focus group discussions and semi-structured interviews with health workers and trainers; (iii) training observations; and (iv) pre- and post-training questionnaires. These methods were used to compare pre- and post-intervention groups and assess differences between the two training rounds. RESULTS: Between 2004 and 2007, local government officials trained 429 health workers. The training was well implemented and over time, trainers' confidence and ability to lead sessions improved. The district-led training significantly improved knowledge relating to HIV/AIDS and puberty (RR ranged from 1.06 to 2.0), attitudes towards condoms, confidentiality and young people's right to treatment (RR range: 1.23-1.36). Intervention health units scored higher in the family planning and condom request simulated patient scenarios, but lower in the sexually transmitted infection scenario than the control health units. The scale up faced challenges in the selection and retention of trained health workers and was limited by various contextual factors and structural constraints. CONCLUSIONS: Youth-friendly services interventions can remain well delivered, even after expansion through existing systems. The scaling-up process did affect some aspects of intervention quality, and our research supports others in emphasizing the need to train more staff (both clinical and non-clinical) per facility in order to ensure youth-friendly services delivery. Further research is needed to identify effective strategies to address structural constraints and broader social norms that hampered the scale up

Synthesis of the originally proposed structures of elatenyne and an enyne from Laurencia majuscula

A bidirectional synthesis of the originally proposed structures for the natural products elatenyne and a chloroenyne from Laurencia majuscula is described along with a reassessment of the structures of the halogenated enynes based upon a C-13 NMR chemical shift/structure correlation

Explicit factorization of external coordinates in constrained Statistical Mechanics models

If a macromolecule is described by curvilinear coordinates or rigid constraints are imposed, the equilibrium probability density that must be sampled in Monte Carlo simulations includes the determinants of different mass-metric tensors. In this work, we explicitly write the determinant of the mass-metric tensor G and of the reduced mass-metric tensor g, for any molecule, general internal coordinates and arbitrary constraints, as a product of two functions; one depending only on the external coordinates that describe the overall translation and rotation of the system, and the other only on the internal coordinates. This work extends previous results in the literature, proving with full generality that one may integrate out the external coordinates and perform Monte Carlo simulations in the internal conformational space of macromolecules. In addition, we give a general mathematical argument showing that the factorization is a consequence of the symmetries of the metric tensors involved. Finally, the determinant of the mass-metric tensor G is computed explicitly in a set of curvilinear coordinates specially well-suited for general branched molecules.Comment: 22 pages, 2 figures, LaTeX, AMSTeX. v2: Introduccion slightly extended. Version in arXiv is slightly larger than the published on

N 3,N 6,2,5,7-Penta­phenyl-2,5,7-triaza­bicyclo­[2.2.1]heptane-3,6-diamine

In the title compound, C34H31N5, the observed molecular geometry suggests that anomeric effects are present in terms of short C—N bond lengths and reduced pyramidality of the N atoms

Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria

A series of N-phenyl-2,5-dimethylpyrrole derivatives, designed as hybrids of the antitubercular agents BM212 and SQ109, have been synthesized and evaluated against susceptible and drug-resistant mycobacteria strains. Compound 5d, bearing a cyclohexylmethylene side chain, showed high potency against M. tuberculosis including MDR-TB strains at submicromolar concentrations. The new compound shows bacteriostatic activity and low toxicity and proved to be effective against intracellular mycobacteria too, showing an activity profile similar to isoniazid