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In this paper, we report a knowledge-based potential function, named the OPUS-Ca potential, that requires only Ca positions as input. The contributions from other atomic positions were established from pseudopositions artificially built from a Ca trace for auxiliary purposes. The potential function is formed based on seven major representative molecular interactions in proteins: distance-dependent pairwise energy with orientational preference, hydrogen bonding energy, short-range energy, packing energy, tri-peptide packing energy, three-body energy, and solvation energy. From the testing of decoy recognition on a number of commonly used decoy sets, it is shown that the new potential function outperforms all known Ca-based potentials and most other coarse-grained ones that require more information than Ca positions. We hope that this potential function adds a new tool for protein structural modeling.Keywords: knowledge-based potential function; decoy recognition; structure prediction; protein folding Protein folding is one of the most challenging problems in both computational and experimental biophysics (Dobson and Karplus 1999). The goal is to determine threedimensional structures from one-dimensional amino acid sequences. In computational studies, a potential function plays a central role in accurately predicting the structures. There are two general types of potential functions: One is physics-based and another is knowledge-based. The physics-based potential functions are derived from quantum mechanical calculations, e.g., the CHARMM force field (MacKerell et al. 1998), the essence of which is molecular mechanics. The knowledge-based potential functions are derived from statistical analysis of known protein structures, the essence of which is the potential of mean force, or free energy. In many applications, it has been shown that the knowledge-based potential functions outperform the physics-based ones. There are many comprehensive reviews for various potential functions in the literature

Dynein light chain 1 (DLC1, also known as DYNLL1, LC8, and PIN), a ubiquitously expressed and highly conserved protein, participates in a variety of essential intracellular events. Transition of DLC1 between dimer and monomer forms might play a crucial role in its function. However, the molecular mechanism(s) that control the transition remain unknown. DLC1 phosphorylation on Ser 88 by p21-activated kinase 1 (Pak1), a signaling nodule, promotes mammalian cell survival by regulating its interaction with Bim and the stability of Bim. Here we discovered that phosphorylation of Ser 88 , which juxtapose each other at the interface of the DLC dimer, disrupts DLC1 dimer formation and consequently impairs its interaction with Bim. Overexpression of a Ser 88 phosphorylation-inactive DLC1 mutant in mammary epithelium cells and in a transgenic animal model caused apoptosis and accelerated mammary gland involution, respectively, with increased Bim levels. Structural and biophysical studies suggested that phosphorylation-mimicking mutation leads to dissociation of the DLC1 dimer to a pure folded monomer. The phosphorylation-induced DLC1 monomer is incapable of binding to its substrate Bim. These findings reveal a previously unrecognized regulatory mechanism of DLC1 in which the Ser 88 phosphorylation acts as a molecular switch for the transition of DLC1 from dimer to monomer, thereby modulating its interaction with substrates and consequently regulating the functions of DLC1.Dyneins are massive minus-to-plus end microtubules motor complexes. Dyneins are categorized into axonemal dyneins and cytoplasmic dyneins on the basis of structural and functional features (1). Cytoplasmic dyneins are essential for a variety of fundamental intracellular events, such as organization and orientation of the mitotic spindle, nuclear migration, Golgi dynamics, retrograde neuronal axonal transport, and trafficking of vesicles and molecules (2-4). Dynein light chain 1 (DLC1) 4 (also known as DYNLL1, LC8, DLC8, and PIN), a ubiquitously expressed 89-amino acid protein, was initially identified as a light chain of the Chlamydomonas outer dynein arm (5). DLC1 is highly conserved from nematodes to mammals, and DLC1 orthologues share more than 90% sequence identity (6). DLC1 binds to a diverse array of proteins and RNAs, including neuronal nitric-oxide synthase (7), IB␣ (8), p53-binding protein 1 (9), GKAP (10), gephyrin postsynaptic scaffolding proteins (11), Bim (12), Swallow (13), estrogen receptor (14), KIBRA (15), CDK2 (16), virus proteins (17, 18), parathyroid hormone mRNA (19), and possibly other proteins (20, 21).Although DLC1 has been shown to bind to many partners, its physiological roles and the upstream regulators of DLC1 remain poorly understood. DLC1 is presumed to have essential cell functions because of its extraordinary sequence conservation across species and ubiquitous expression. Genetic studies in Aspergillus suggested that DLC1 is important for activities of dynein, because a DLC1 temperature-sensitive mutation led to multiple d...

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