Molecular force fields have been approaching a generational transition over the past several years, moving away from well-established and well-tuned, but intrinsically limited, fixed point charge models towards more intricate and expensive polarizable models that should allow more accurate description of molecular properties. The recently introduced AMOEBA force field is a leading publicly available example of this next generation of theoretical model, but to date has only received relatively limited validation, which we address here. We show that the AMOEBA force field is in fact a significant improvement over fixed charge models for small molecule structural and thermodynamic observables in particular, although further fine-tuning is necessary to describe solvation free energies of drug-like small molecules, dynamical properties away from ambient conditions, and possible improvements in aromatic interactions. State of the art electronic structure calculations reveal generally very good agreement with AMOEBA for demanding problems such as relative conformational energies of the alanine tetrapeptide and isomers of water sulfate complexes. AMOEBA is shown to be especially successful on protein-ligand binding and computational X-ray crystallography where polarization and accurate electrostatics are critical.

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Fertilization in humans is initiated by binding of spermatozoa to a selectin ligand on the egg’s extracellular matrix.

Glycodelin, also known as placental protein 14 (PP14) or progesterone-associated endometrial protein (PAEP), is a human glycoprotein with potent immunosuppressive and contraceptive activities. In this paper we report the first characterization of glycodelin-derived oligosaccharides. Using strategies based upon fast atom bombardment and electrospray mass spectrometry we have established that glycodelin is glycosylated at Asn-28 and Asn-63. The Asn-28 site carries high mannose, hybrid and complex-type structures, whereas the second site is exclusively occupied by complex-type glycans. The major non-reducing epitopes in the complextype glycans are: Gal␤1-4GlcNAc (lacNAc), GalNAc␤1-4GlcNAc (lacdiNAc), NeuAc␣2-6Gal␤1-4GlcNAc (sialylated lacNAc), NeuAc␣2-6GalNAc␤1-4GlcNAc (sialylated lacdiNAc), Gal␤1-4(Fuc␣1-3)GlcNAc (Lewis x ), and GalNAc␤1-4(Fuc␣1-3)GlcNAc (lacdiNAc analogue of Lewis x ). It is possible that the oligosaccharides bearing sialylated lacNAc or lacdiNAc antennae may manifest immunosuppressive effects by specifically blocking adhesive and activation-related events mediated by CD22, the human B cell associated receptor. Oligosaccharides with fucosylated lacdiNAc antennae have previously been shown to potently block selectin-mediated adhesions and may perform the same function in glycodelin. The potent inhibitory effect of glycodelin on initial human sperm-zona pellucida binding is consistent with our previous suggestion that this cell adhesion event requires a selectin-like adhesion process. This result also raises the possibility that a convergence between immune and gamete recognition processes may have occurred in the types of carbohydrate ligands recognized in the human.