Biomedical subjects

Mark L Benson

Publications and source records attributed to Mark L Benson.

4 recordsLinked to original sources

PubMed2005

Exploring protein-ligand recognition with Binding MOAD.

We have recently announced the largest database of protein-ligand complexes, Binding MOAD (Mother of All Databases). After the August 2004 update, Binding MOAD contains 6816 complexes. There are 2220 protein families and 3316 unique ligands. After searching 6000+ crystallography papers, we have obtained binding data for 1793 (27%) of the complexes. We have also created a non-redundant set of complexes with only one complex from each protein family; in that set, 630 (28%) of the unique complexes have binding data. Here, we present information about the data provided at the Binding MOAD website. We also present the results of mining Binding MOAD to map the degree of solvent exposure for binding sites. We have determined that most cavities and ligands (70-85%) are well buried in the complexes. This fits with the common paradigm that a large degree of contact between the ligand and protein is significant in molecular recognition. GoCAV and the GoCAV viewer are the tools we created for this study. To share our data and make our online dataset more useful to other research groups, we have integrated the viewer into the Binding MOAD website (www.BindingMOAD.org).

Binding Sites↗

PubMed2005

Binding MOAD (Mother Of All Databases).

Binding MOAD (Mother of All Databases) is the largest collection of high-quality, protein-ligand complexes available from the Protein Data Bank. At this time, Binding MOAD contains 5331 protein-ligand complexes comprised of 1780 unique protein families and 2630 unique ligands. We have searched the crystallography papers for all 5000+ structures and compiled binding data for 1375 (26%) of the protein-ligand complexes. The binding-affinity data ranges 13 orders of magnitude. This is the largest collection of binding data reported to date in the literature. We have also addressed the issue of redundancy in the data. To create a nonredundant dataset, one protein from each of the 1780 protein families was chosen as a representative. Representatives were chosen by tightest binding, best resolution, etc. For the 1780 "best" complexes that comprise the nonredundant version of Binding MOAD, 475 (27%) have binding data. This significant collection of protein-ligand complexes will be very useful in elucidating the biophysical patterns of molecular recognition and enzymatic regulation. The complexes with binding-affinity data will help in the development of improved scoring functions and structure-based drug discovery techniques. The dataset can be accessed at http://www.BindingMOAD.org.

Biophysics↗

PubMed2002

The importance of radiation doses to the penile bulb vs. crura in the development of postbrachytherapy erectile dysfunction.

PURPOSE: Recent studies have implicated the proximal penis as a potential site-specific structure for radiation-related erectile dysfunction (ED). In this study, we evaluated by means of a validated patient-administered questionnaire whether radiation doses to the bulb of the penis and/or the proximal corporeal bodies were predictive for the development of brachytherapy-induced ED. METHODS AND MATERIALS: Thirty patients who underwent permanent prostate brachytherapy between April 1995 and October 1999 and developed brachytherapy-induced ED were paired with 30 similar men who maintained potency after implantation. None of the 60 patients received supplemental external beam radiation therapy, either before or after implantation. Potency was assessed by patient self-administration of the specific erectile questions of the International Index of Erectile Function. The questionnaire consisted of 5 questions with a maximum score of 25. Postimplant potency was defined as an International Index of Erectile Function score > or =11. Mean and median follow-up was 48.3 +/- 14.4 months and 48.0 months, respectively (range: 26.6-79.3 months). The bulb of the penis and the proximal crura were outlined at 0.5-cm intervals on the Day 0 postimplant CT scan. The radiation dose distribution to the bulb of the penis and adjacent crura was defined in terms of the minimum dose delivered to 25%, 50%, 70%, 75%, 90%, and 95% of the bulb (D(25), D(50), D(70), D(75), D(90), and D(95)). RESULTS: The radiation dose delivered to the bulb of the penis and the proximal crura in men with brachytherapy-induced ED was statistically greater for all evaluated dosimetric parameters (D(25), D(50), D(70), D(75), D(90), and D(95)). Stepwise linear regression analysis indicated that penile bulb dose parameter D(50), the postimplant prostate CT volume, and patient age at implant were predictive of postimplant ED, whereas the crura dose D(25) approached statistical significance. Seventy-five percent of the impotent men had a bulb D(25) >60% of prescribed minimum peripheral dose (mPD), whereas 80% of potent men had a bulb D(25) < or =60% mPD. Using the D(50) bulb parameter, 70% of ED men had a dose >40% mPD, whereas 90% of potent men had a dose < or =40% mPD. Similar cut points for D(25) and D(50) crura doses were 40% and 28% mPD. The crura D(25) cut point was exceeded by 50% of the ED patients and only 7% of the potent patients. CONCLUSION: This is the first study to evaluate potency preservation and radiation doses to the proximal penis by means of a validated patient-administered quality-of-life instrument. Our data confirm prior reports that radiation doses to the proximal penis are predictive of brachytherapy-induced ED. In a stepwise linear regression analysis, the strongest predictors of potency preservation were bulb D(50), postimplant prostate CT volume, and patient age. With Day 0 dosimetric evaluation, the penile bulb D(50) and D(25) should be maintained below 40% and 60% mPD, respectively, whereas the crura D(50) and D(25) should be maintained below 40% and 28% mPD, respectively, to maximize posttreatment potency.

Age Factors↗

PubMed2002

Penile bulb imaging.

PURPOSE: Because of the apparent relationship between potency loss and radiation doses to the erectile bodies, there is increasing rationale for incorporating penile bulb dosimetry into treatment planning and posttreatment evaluation. Because the location and shape of the penile bulb have not been described in detail on various imaging modalities, we herein describe the anatomic boundaries of the penile bulb on computed tomography (CT), magnetic resonance imaging (MR), and transrectal ultrasound (TRUS), before and after brachytherapy. METHODS AND MATERIALS: Nonenhanced axial CT images were taken on a CTi CT Scanner (General Electric Medical Systems, Milwaukee, WI) with the patient in the supine position. Settings were at 300 ma, 140 kvp, 4-s scan time per slice, and collimation of 3 mm with data obtained at 3-mm intervals. Nonenhanced MR images were obtained with a 1.5 Tesla Signa Horizon LX Scanner using fast spin-echo T1-weighted (TR/TE, 466/20) and T2-weighted (TR/TE, 8000/90) images, with a slice thickness of 2 mm and an interslice gap of 0.5 mm. TRUS images were obtained with a Siemens SONOLINE Prima ultrasound machine at 6.0 MHz and a Winston-Barzell stepper unit. RESULTS: The penile bulb is best visualized on T2-weighted MR images in the axial, sagittal, and coronal planes, appearing as an oval-shaped, hyperintense midline structure. On axial CT imaging, the bulb of the penis is typically readily identifiable, bounded by the paired crura laterally, the corpora spongiosum anteriorly, and the levator ani posteriorly. The penile bulb is typically well visualized on transverse TRUS, but usually only faintly seen on sagittal TRUS. The bulb is partially obscured on postimplant CT and MR images, presumably because of implant-related edema. Bulb volumes vary markedly from patient to patient, ranging from 5.6 to 12.4 cc (median: 8.1 cc). CONCLUSION: Closer attention to penile erectile tissue doses should lead to improved external beam radiation and brachytherapy delivery. It will benefit the radiation oncology community to become familiar with these imaging findings, so that penile bulb dosimetry can be incorporated into our daily practice.

Humans↗