Biomedical subjects

A N Jain

Publications and source records attributed to A N Jain.

8 recordsLinked to original sources

PubMed1996

Hammerhead: fast, fully automated docking of flexible ligands to protein binding sites.

BACKGROUND: Molecular docking seeks to predict the geometry and affinity of the binding of a small molecule to a given protein of known structure. Rigid docking has long been used to screen databases of small molecules, because docking techniques that account for ligand flexibility have either been too slow or have required significant human intervention. Here we describe a docking algorithm, Hammerhead, which is a fast, automated tool to screen for the binding of flexible molecules to protein binding sites. RESULTS: We used Hammerhead to successfully dock a variety of positive control ligands into their cognate proteins. The empirically tuned scoring function of the algorithm predicted binding affinities within 1.3 log units of the known affinities for these ligands. Conformations and alignments close to those determined crystallographically received the highest scores. We screened 80 000 compounds for binding to streptavidin, and biotin was predicted as the top-scoring ligand, with other known ligands included among the highest-scoring dockings. The screen ran in a few days on commonly available hardware. CONCLUSIONS: Hammerhead is suitable for screening large databases of flexible molecules for binding to a protein of known structure. It correctly docks a variety of known flexible ligands, and it spends an average of only a few seconds on each compound during a screen. The approach is completely automated, from the elucidation of protein binding sites, through the docking of molecules, to the final selection of compounds for assay.

Algorithms↗

PubMed1995

Quantitative binding site model generation: compass applied to multiple chemotypes targeting the 5-HT1A receptor.

We present enhancements to the Compass algorithm that automatically deduce interchemotype relationships and generate predictive quantitative models of receptor binding based solely on structure-activity data. We applied the technique to a series of compounds assayed for 5-HT1A binding. A model was constructed from 20 compounds of two chemotypes and used to predict the affinities and bioactive conformation of 35 new compounds, most of which had new underlying scaffolds and/or functional groups. The model's mean error of prediction was 0.5 log units (essentially the assay resolution), even on quite divergent series. The predictions are supported by an interpretable hypothesis for the binding determinants of the receptor and the geometric relationships of the chemotypes.

Algorithms↗

PubMed1994

Compass: predicting biological activities from molecular surface properties. Performance comparisons on a steroid benchmark.

We describe a new method, Compass, for predicting the biological activities of molecules based on the activities and three-dimensional structures of other molecules. The method improves on previous techniques by representing only the surface of molecules, by incorporating a nonlinear statistical method, and by automatically choosing conformations and alignments of molecules. We use a benchmark problem of steroid binding affinity prediction to compare the performance of the method with that of two previous systems: CoMFA and a molecular similarity method. Compass predicts steroid affinities substantially more accurately than the others, which represent the state of the art. We present experiments showing that the improved performance depends on each of the technical innovations.

Algorithms↗

PubMed1994

A shape-based machine learning tool for drug design.

Building predictive models for iterative drug design in the absence of a known target protein structure is an important challenge. We present a novel technique, Compass, that removes a major obstacle to accurate prediction by automatically selecting conformations and alignments of molecules without the benefit of a characterized active site. The technique combines explicit representation of molecular shape with neural network learning methods to produce highly predictive models, even across chemically distinct classes of molecules. We apply the method to predicting human perception of musk odor and show how the resulting models can provide graphical guidance for chemical modifications.

Algorithms↗

PubMed1981

Quality control of dose calibrators.

Radionuclide dose calibrators are instruments that require regular checks and proper usage to ensure that they are operating correctly. The responsibility for the accuracy of the activity and the resultant estimate of the dose delivered to the patient rests with the persons administering the radiopharmaceutical. Hence, it is essential that accurate measurements of radioactivity be provided by the dose calibrator in use in every nuclear medicine department. The routine testing of the calibrator would ensure the user that the overall characteristics of the instrument are within acceptable limits. The quality control of two dose calibrators was carried out elaborately and their performance was evaluated from various aspects of quality control such as geometry effect, instrument linearity, precision test, instrument accuracy etc. It was found that one of the calibrators was having non-linear response resulting in an error of 18% from the decay-predicted activity. It also showed a saturation effect beyond 310 mCi. Hence, it needed repair or recalibration. However, the other calibrator was working satisfactorily. This study also helped us in realizing certain operational pitfalls of the dose calibrators.

Dose-Response Relationship, Radiation↗

PubMed1981

Pitfalls in the lateral imaging of the thyroid with pinhole collimators.

Imaging of the thyroid gland with pinhole collimators in the lateral projection is associated with the problem of count rate contribution from the contralateral lobe. In a series of experiments conducted using a thyroid-simulating phantom, the contribution of this nature was calculated. Radioisotopes of different energies such as 99mTc and 131I were used to see the effect of energy on this contribution. It was observed that the count rate contribution from the contralateral lobe to the lobe proximal to the collimator can be as high as 70% at a distance of 6 cm from the collimator. At distances more than 6 cm these contributions from the contralateral lobe are much more than this.

Iodine Radioisotopes↗

PubMed1980

Scan appearances in hydatid cysts of the liver: analysis of 55 cases.

Liver scans done at our Centre between 1964 and 1977 were analyzed with reference to hydatid cysts in liver. Among the approximately 7200 patients analyzed, there were 55 suspected to have hydatid cysts. The criteria adopted in screening the patients for hydatid cysts were based upon clinical findings and liver scan findings. The cases were analyzed with respect to their histologic findings, locations of cold areas in the liver, and correlation with Casoni's test. We found that 1) the cystic involvement was most often in the right lobe of the liver; 2) Casoni's test does not rule out or establish the presence of hydatidosis; 3) radioisotopic vascular studies done in some cases contributed to the diagnosis; 4) although a positive liver scan does not indicate the cause of the disease, the scans showing large and totally photon-deficient cold areas along with good general condition of the patients help in the diagnosis of hydatid cysts in the liver.

Colloids↗

PubMed1978

Efficacy of brain scanning in epilepsy of late onset.

Brain scans of 513 patients with epilepsy of late onset were analysed with reference to the patient's age and sex and to the nature of convulsion. Only 17 of them showed an abnormal concentration of radionuclide indicating a space-occupying lesion in the brain. The findings of those patients who had positive brain scans were correlated with EEG findings. It was found that the incidence of epilepsy of late onset is almost 3 times higher in males than in females and that the age cannot be considered as a criterion for screening the patients for brain scan investigations as far as epilepsy of late onset is concerned. In our opinion, the incidence of 3.3% is not too low. A positive brain scan finding calls for further investigation and helps in deciding the management and further line of treatment of the patients. Moreover, a normal scan rules out the presence of a space-occupying lesion and helps as a screening procedure.

Adult↗