Validation of molecular dynamics simulation

How the results obtained by computer simulation of molecular systems can be validated is considered. The overall quality of the simulated properties of a molecular system will depend on (i) the quality of the theory or model, (ii) the accuracy of the interatomic interaction function or force field, (iii) the degree of sampling, statistics and convergence reached in the simulation, (iv) the quality of the simulation software, and (v) how competently the simulation software is used. These five validation issues are discussed and illustrated with examples. Guidelines for different members of the scientific community are formulated which are aimed at enabling and improving the validation of simulation results in the literature. © 1998 American Institute of Physics

Long-term perturbations due to a disturbing body in elliptic inclined orbit

In the current study, a double-averaged analytical model including the action of the perturbing body's inclination is developed to study third-body perturbations. The disturbing function is expanded in the form of Legendre polynomials truncated up to the second-order term, and then is averaged over the periods of the spacecraft and the perturbing body. The efficiency of the double-averaged algorithm is verified with the full elliptic restricted three-body model. Comparisons with the previous study for a lunar satellite perturbed by Earth are presented to measure the effect of the perturbing body's inclination, and illustrate that the lunar obliquity with the value 6.68\degree is important for the mean motion of a lunar satellite. The application to the Mars-Sun system is shown to prove the validity of the double-averaged model. It can be seen that the algorithm is effective to predict the long-term behavior of a high-altitude Martian spacecraft perturbed by Sun. The double-averaged model presented in this paper is also applicable to other celestial systems.Comment: 28 pages, 6 figure

pKa Modulation of the Acid/Base Catalyst within GH32 and GH68: A Role in Substrate/Inhibitor Specificity?

Glycoside hydrolases of families 32 (GH32) and 68 (GH68) belong to clan GH-J, containing hydrolytic enzymes (sucrose/fructans as donor substrates) and fructosyltransferases (sucrose/fructans as donor and acceptor substrates). In GH32 members, some of the sugar substrates can also function as inhibitors, this regulatory aspect further adding to the complexity in enzyme functionalities within this family. Although 3D structural information becomes increasingly available within this clan and huge progress has been made on structure-function relationships, it is not clear why some sugars bind as inhibitors without being catalyzed. Conserved aspartate and glutamate residues are well known to act as nucleophile and acid/bases within this clan. Based on the available 3D structures of enzymes and enzyme-ligand complexes as well as docking simulations, we calculated the pKa of the acid-base before and after substrate binding. The obtained results strongly suggest that most GH-J members show an acid-base catalyst that is not sufficiently protonated before ligand entrance, while the acid-base can be fully protonated when a substrate, but not an inhibitor, enters the catalytic pocket. This provides a new mechanistic insight aiming at understanding the complex substrate and inhibitor specificities observed within the GH-J clan. Moreover, besides the effect of substrate entrance on its own, we strongly suggest that a highly conserved arginine residue (in the RDP motif) rather than the previously proposed Tyr motif (not conserved) provides the proton to increase the pKa of the acid-base catalyst

Evolution of the Developmental Scores of 16 Morphological Features in Mouse Embryos Displaying 0 To 30 Somites

A precise framework of morphological developmental events observed macroscopically in early postimplantation mouse embryos aged 8-10 days (0-30 somites) is established. The quantitative evolution of the developmental score of 16 features as a function of the developmental stage of the embryos (expressed in number of somites) is presented. Thirty-one groups of ten embryos, each with 0 to 30 somites, were scored for each feature according to the previous description of the authors. In addition, the variation of individual structures as a function of embryonic developmental stages is evaluated. It is suggested that the framework of differentiating individual structures at given developmental stages will help to plan experiments in developmental biology of rodents and will facilitate the interpretation of results in developmental toxicity

Evolution of the developmental scores of sixteen morphological features in mouse embryos displaying 0 to 30 somites.

A precise framework of morphological developmental events observed macroscopically in early postimplantation mouse embryos aged 8-10 days (0-30 somites) is established. The quantitative evolution of the developmental score of 16 features as a function of the developmental stage of the embryos (expressed in number of somites) is presented. Thirty-one groups of ten embryos, each with 0 to 30 somites, were scored for each feature according to the previous description of the authors. In addition, the variation of individual structures as a function of embryonic developmental stages is evaluated. It is suggested that the framework of differentiating individual structures at given developmental stages will help to plan experiments in developmental biology of rodents and will facilitate the interpretation of results in developmental toxicity

Assessment of nuclear totipotency of fetal bovine diploid germ cells by nuclear transfer.

Nuclear transfer was used to study nuclear reprogramming of fetal diploid bovine germ cells collected at two stages of the fetal development. In the first case, germ cells of both sexes were collected during their period of intragonadal mitotic multiplication at 48 days post coitum (d.p.c.). In the second case, only male germ cells were collected after this period, between 105 and 185 d.p.c. Isolated germ cells were fused with enucleated oocytes. Reconstituted embryos were cultured in vitro and those reaching the compacted morula or blastocyst stage were transferred into synchronous recipient heifers. Of 511 reconstituted embryos with 48 d.p.c. germ cells (309 males and 202 females), 48% (247/511 ) cleaved; 2.7% (14/511 ) reached the compacted morula stage and 8 of them the blastocyst stage (1.6%). No difference was observed between sexes. All 14 compacted morulae/blastocysts were transferred into 6 recipients and one pregnancy was initiated. This recipient was slaughtered at Day 35 and an abnormal conceptus (extended trophectoderm and degenerated embryo) was collected. Its male sex, genetically determined, corresponded to that of donor fetus. Of 380 reconstituted embryos with male 105 to 185 d.p.c. germ cells, 72.1% (274/380 ) cleaved, 2.1% (8 380 ) reached the compact morula stage and 7 of these the blastocyst stage (1.8%). Three blastocysts and one morula were transferred into 4 recipients. Two became pregnant at Day 21 but only one at Day 35 which aborted around Day 40. Our results show that the nucleus of diploid bovine germ cells of both sexes can be reprogrammed. However, in the absence of further development of these reconstituted embryos, nuclear totipotency of bovine diploid germ cells remains to be evidenced