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Biomedical subjects

E Platt

Publications and source records attributed to E Platt.

14 recordsLinked to original sources
PubMed2005

Factors related to the process of seeking and completing treatment for drug abuse (qualitative methods in drug abuse research).

Numerous studies have demonstrated the effectiveness of drug abuse treatment. Yet many drug abusers do not enter treatment, many who do enter leave prematurely, and relapse following treatment is common. Understanding motivation for change and treatment readiness is key to understanding how to induct and engage drug users in treatment. To the extent that treatment programs focus initially on reducing drug use, rather than psychosocial problems that motivate individuals to seek treatment, treatment programs may fail to meet the primary needs of users and thus fail to attract or engage them. Outcomes of substance abuse treatment programs historically have been measured by successful program completion, reduced drug use and illegal activity, and improved social functioning (employment, education etc). There is minimal reference to client expectations of treatment and factors that influenced treatment-seeking behavior. Studies that have assessed client dropout from substance abuse treatment have generally focused upon quantitative measures that attempt to determine what types of clients drop out or stay, or what types of characteristics best predict client dropout. Qualitative methods are the most appropriate to fill these gaps in substance abuse treatment research.

Humans↗
PubMed1994

Novel algorithms for searching conformational space.

The modelling of biological molecules by molecular dynamics is beset by a range of problems. The most important of these is the multiple-minima problem. The deep metastable minima can cause difficulties in proper equilibration of a molecular system and result in the simulated system being trapped in a long-lived metastable state. One way to overcome these problems is to re-engineer the 'Newtonian Rules' in order to more efficiently search conformational space. Re-engineering of the 'Newtonian Rules' implies a redesign of the physical laws arising from them. This is done in various ways by the RUSH, Hybrid Monte Carlo and PEACS algorithms. This paper explores applications of these algorithms, and compares them to a traditional molecular dynamics method.

Alanine↗
PubMed1993

Acetylation phenotype and genotype in aboriginal leprosy patients from the north-west region of Western Australia.

N-Acetyltransferases (NAT1, NAT2) play an important role in biotransformation of a number of drugs and carcinogens. A polymorphism in the metabolism of such compounds by NAT2 has been known for many years but it is only recently that the underlying molecular genetics has been elucidated. In the present study, we have correlated acetylation phenotype and genotype in a group of 49 Australian Aborigines (26 males and 23 females; mean age = 50.5 yr) from the Derby region of Western Australia. Phenotype was determined using caffeine and genotype by an allele-specific polymerase chain reaction. The percentages of slow and rapid phenotypes were 36.7 and 63.3%, respectively, while the distribution of alleles for the NAT2 gene was 41% for the wildtype and 2, 17 and 40% for the M1, M2 and M3 mutations, respectively. This is the highest proportion of M3 mutations reported for any ethnic population. The observed genotype proportions were not significantly different from those predicted by the Hardy-Weinberg Law (chi 2 = 1.07, p > 0.05). Phenotype was predictable from genotype in 100% of patients. At the time of study, 29 of the Aborigines were receiving acedapsone intramuscularly for control of leprosy. Plasma dapsone concentrations in these patients were similar for both slow (n = 11) and rapid (n = 18) acetylators, suggesting that phenotype is unlikely to influence treatment outcome. The data show that Aborigines have a similar phenotype distribution to that of some Asian populations, but that there are differences in the frequencies of the M1, M2 and M3 mutant alleles.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1991

Development and testing of protocols for computer-aided design of peptide drugs, using oxytocin.

Considerable clinical interest in neuropeptides and peptide hormones has stimulated recent research and development of peptide-based drugs. This process differs from most classical drug discovery procedures because peptide molecules have considerable inherent flexibility. In the present paper, to identify lowest energy and metastable conformers for drug design, and to develop protocols for such studies, conformational search algorithms, incorporating empirical energy calculations, have been applied in the analysis of the peptide oxytocin. Energy minimization in torsion angle space was carried out from a variety of starting conformations, including published structures, in all-atom mode and all with distance constraints for disulphide bond formation. The energy-minimized conformations have been further optimized by a mapping method. Complementary simulations have been performed in united-atom mode and a model representing the effects of water using dummy sites has been developed and tested for this representation. Several of the preferred conformers together with de novo conformations have been used as starting points in molecular dynamics simulations; 28 low potential energy conformations were located at a temperature of 4 K. Conformations are analysed to identify hydrogen bonds, phi-psi angle distributions and the RMS values relative to the X-ray structure of deamino-oxytocin. The modelled structure of lowest energy in the molecular mechanics calculations was also that of least RMS deviation from the crystal structure; whilst structures of lower energy but larger deviation were identified by molecular dynamics techniques. A metastable structure has been identified which satisfies existing criteria for the "active form", and this model is tested by a theoretical residue-substitution technique, to provide clues on the agonist/antagonist relationship at the atomic level.

Computers↗
PubMed1990

Comparison of the X-ray structure of baboon alpha-lactalbumin and the tertiary predicted computer models of human alpha-lactalbumin.

The previously predicted structures of human alpha-lactalbumin by homology with hen egg white lysozyme by an automatic method, after the alignment stage, are compared to the X-ray determined structure of baboon alpha-lactalbumin. The root mean square by rotation method (RMSR) deviations for 122 C-alpha atoms between the two models and the X-ray structure are 2.0 A and 2.3 A. The RMSR deviations for all atoms, except for differences in human and baboon sequences, are 2.8 A and 3.1 A. If the flexible C-terminus (residues 112-122) are removed then these RMSR deviations are reduced to 2.4 A and 2.3 A respectively. These results are consistent with the fact that the RMSR deviation between the human and baboon X-ray structures increases from residue 112 onwards and is conformationally flexible.

Amino Acid Sequence↗
PubMed1990

The expert system approach to predicting protein structure.

Prediction of protein structure is an open-ended problem. Since an approach from first principles cannot be taken in reasonable computer time, short-cuts using further data are necessary. Such data include information about the specific protein in question, and information in databases which are about proteins in general. Is it possible to write a general, flexible 'superalgorithm' which would suit most circumstances? If so, it would seem likely to overcome one of the most understated but nonetheless greatest difficulties associated with molecular modelling and computer-aided drug design--reproducibility. To this end, a 'polymorphic programming environment' has been developed which represents both an expert system and a high-level language for theoretical chemists and molecular biologists. This language is GLOBAL (Ball et al., 1990). In a series of earlier studies, and more recently by means of GLOBAL itself, the nature of reproducibility and its rather surprising limits have been explored, and in general the current status and future potential of protein modelling have been examined.

Expert Systems↗
PubMed1987

Modelling of alpha-lactalbumin from the known structure of hen egg white lysozyme using molecular dynamics.

The prediction of protein conformation by homology is being widely pursued using interactive computer graphics. However, there have been a limited number of energy minimization and/or molecular dynamics studies for such predictions. This paper reports one such study on alpha-lactalbumin, a system that can be tested as the X-ray crystal structure has recently been determined. The differences in structure of the Ca2+ binding loop reported for the holo-protein (Stuart et al., Nature, 324 [1986] 84-87) and that predicted for the apoprotein could be attributed to the presence or absence of the Ca2+ ion.

Animals↗
PubMed1986

Refined models for computer calculations in protein engineering. Calibration and testing of atomic potential functions compatible with more efficient calculations.

A reappraisal has been made of interatomic potential functions for protein structure calculations using the all-atom approximation (except CH, CH2 and CH3, which are treated as "united atoms"). Some key problems are identified and treated. The potential functions are somewhat novel in form and consistent with more efficient and robust folding algorithms. In addition, the potentials are calibrated for for the rigid geometry approximation, since use of fixed standard bond lengths and valence angles (and fixed trans planar peptide groups) reduces the number of conformational variables and saves a great deal of computer time. Though these algorithms demand the use of potential functions of this special type, these functions can be readily implemented in more classical programs for the conformational analysis of proteins. They are calibrated or tested against a large body of experimental data, including extended basis set ab initio, quantum mechanical calculations, nuclear magnetic resonance spectroscopic data and dipole moment data for di- and oligopeptides, characteristic ratio data for random coil homopolypeptides, extensive data from peptide solubility studies, and experimental structures of polyalanine fibres and globular proteins. This paper will form the basis of a further report, which will include investigations of how water might be more realistically represented subject to the computing power available.

Amino Acid Sequence↗
PubMed1985

Prediction of the conformation and antigenic determinants of the V-sis viral oncogene product homologous with human platelet-derived growth factor.

In an extensive study involving unification of secondary structure prediction methods to predict peptide backbone angles, folding simulations, and interactive graphics we have calculated conformations for a 160 residue p28sis protein fragment. We demonstrate that the state of the art is sufficient to aid artificial vaccine design.

Antigens, Viral↗
PubMedDate not supplied

Let's get physical!

As part of Michigan's health care leadership team, people look to you to provide quality, health-related services to them and their families--a duty you do your best to fulfill. Unfortunately, you are so busy serving their health needs that you neglect your own.

Exercise↗