Biomedical subjects

D E Konerding

Publications and source records attributed to D E Konerding.

4 recordsLinked to original sources

PubMed2000

The Ensemble/Legacy Chimera extension: standardized user and programmer interface to molecular Ensemble data and Legacy modeling programs.

Ensemble/Legacy is a toolkit extension of the Object Technology Framework (OTF) that exposes an object oriented interface for accessing and manipulating ensembles (collections of molecular conformations that share a common chemical topology) and driving Legacy programs (such as MSMS, AMBER, X-PLOR, CORMA/MARDIGRAS, Dials and Windows, and CURVES). Ensemble/Legacy provides a natural programming interface for running Legacy programs on ensembles of molecules and accessing the resulting data. Using the OTF reduces the time cost of developing a new library to store and manipulate molecular data and also allows Ensemble/Legacy to integrate into the Chimera visualization program. The extension to Chimera exposes the Legacy functionality using a graphical user interface that greatly simplifies the process of modeling and analyzing conformational ensembles. Furthermore, all the C++ functionality of the Ensemble/Legacy toolkit is "wrapped" for use in the Python programming language. More detailed documentation on using Ensemble/Legacy is available online (http:¿picasso.nmr.ucsf.edu/dek/ensemble. html).

Computer Graphics↗

PubMed1999

Restrained molecular dynamics of solvated duplex DNA using the particle mesh Ewald method.

Restrained and unrestrained aqueous solution molecular dynamics simulations applying the particle mesh Ewald (PME) method to DNA duplex structures previously determined via in vacuo restrained molecular dynamics with NMR-derived restraints are reported. Without experimental restraints, the DNA decamer, d(CATTTGCATC).d(GATGCAAATG) and trisdecamer, d(AGCTTGCCTTGAG).d(CTCAAGGCAAGCT), structures are stable on the nanosecond time scale and adopt conformations in the B-DNA family. These free DNA simulations exhibit behavior characteristic of PME simulations previously performed on DNA sequences, including a low helical twist, frequent sugar pucker transitions, BI-BII(epsilon-zeta) transitions and coupled crakshaft (alpha-gamma) motion. Refinement protocols similar to the original in vacuo restrained molecular dynamics (RMD) refinements but in aqueous solution using the Cornell et al. force field [Cornell et al. (1995) J. Am. Chem. Soc., 117, 5179-5197] and a particle mesh Ewald treatment produce structures which fit the restraints very well and are very similar to the original in vacuo NMR structure, except for a significant difference in the average helical twist. Figures of merit for the average structure found in the RMD PME decamer simulations in solution are equivalent to the original in vacuo NMR structure while the figures of merit for the free MD simulations are significantly higher. The free MD simulations with the PME method, however, lead to some sequence-dependent structural features in common with the NMR structures, unlike free MD calculations with earlier force fields and protocols. There is some suggestion that the improved handling of electrostatics by PME improves long-range structural aspects which are not well defined by the short-range nature of NMR restraints.

Algorithms↗

PubMed1999

Shape-selective recognition of a model Okazaki fragment by geometrically-constrained bis-distamycins.

Okazaki fragments represent interesting targets for the design of anticancer drugs because of their selective occurrence during DNA replication, a process often elevated in aggressive malignancies. Structural studies have indicated a bend occurs in the helical axis at the junction region (JR) that joins the DNA duplex region (DDR) and the RNA-DNA hybrid duplex region (HDR) of model Okazaki fragments. To identify a structural motif that provides a shape complementary to the Okazaki fragment minor groove, we have investigated the binding of geometrically-constrained bis-distamycins to a model Okazaki fragment, [OKA], with a sequence derived from the genome of simian virus 40 (SV40). Both the JR and the DDR of [OKA] contain consecutive A/T base pairs that could accommodate distamycin binding. Of the six bis-distamycins selected for analysis, the two with a para configuration of the distamycins on the benzene or pyridine scaffold bound [OKA] tightly (Kd approximately 10(-6) M from gel-shift assays; Kd approximately 10(-8) M from deltaT(M)) while the four with a meta orientation did not bind. The two mono-distamycins studied also did not bind [OKA]. Molecular modeling of the complex between the para bis-distamycin MT-9 and [OKA] revealed MT-9 adopted an S- shape complementary to the minor groove of the model Okazaki fragment.

Antineoplastic Agents↗

PubMed1999

Virtual network computing: cross-platform remote display and collaboration software.

VNC (Virtual Network Computing) is a computer program written to address the problem of cross-platform remote desktop/application display. VNC uses a client/server model in which an image of the desktop of the server is transmitted to the client and displayed. The client collects mouse and keyboard input from the user and transmits them back to the server. The VNC client and server can run on Windows 95/98/NT, MacOS, and Unix (including Linux) operating systems. VNC is multi-user on Unix machines (any number of servers can be run are unrelated to the primary display of the computer), while it is effectively single-user on Macintosh and Windows machines (only one server can be run, displaying the contents of the primary display of the server). The VNC servers can be configured to allow more than one client to connect at one time, effectively allowing collaboration through the shared desktop. I describe the function of VNC, provide details of installation, describe how it achieves its goal, and evaluate the use of VNC for molecular modelling. VNC is an extremely useful tool for collaboration, instruction, software development, and debugging of graphical programs with remote users.

Chemistry↗