Computer simulations of the effect of protein dynamics on the long distance tunneling mediated by the protein matrix have been carried out for a Ru-modified (His 126) azurin molecule. We find that the tunneling matrix element is a sensitive function of the atomic configuration of the part of the protein matrix in which tunneling currents (pathways) are localized. Molecular dynamics simulations show that f luctuations of the matrix element can occur on a time scale as short as 10 fs. These short time f luctuations are an indication of a strong dynamic coupling of a tunneling electron to vibrational motions of the protein nuclear coordinates. The latter results in a modification of the conventional Marcus picture of electron transfer in proteins. The new element in the modified theory is that the tunneling electron is capable of emitting or absorbing vibrational energy (phonons) from the medium. As a result, some biological reactions may occur in an activationless fashion. An analytical theoretical model is proposed to account for thermal f luctuations of the medium in long distance electron transfer reactions. The model shows that, at long distances, the phonon-modified inelastic tunneling always dominates over the conventional elastic tunneling.Electron transfer is an integral part of many biological processes, such as photosynthesis and respiration. Much effort, therefore, has been directed toward understanding transport properties of various biological materials. In particular, recent experimental studies have provided information on the distance and structural dependence of electron transfer rates in various natural and modified proteins (1-4). In these systems, electron transfer typically occurs over distances of 10-30 Å and is due to tunneling mediated by the intervening medium between donor and acceptor.It is commonly believed that fundamental principles of long distance electron transfer are essentially the same as those of any other electron transfer reaction (5). The only difference seems to be in the nature of electronic coupling; in short distance reactions, electronic orbitals of donor and acceptor directly overlap whereas in long distance reactions this coupling is indirect because of sequential overlaps of atomic orbitals of the donor, the intervening medium (bridge), and the orbitals of the acceptor. These sequential overlaps give rise to the concept of superexchange. It is assumed that all states in the bridging medium are virtual, i.e., there are no other resonant states in the system but those of donor and acceptor. The resonance between donor and acceptor occurs in the course of thermal fluctuations of the polar environment. The absence of real intermediate states and direct coupling physically means that electron transfer occurs via tunneling. In this picture, the overall rate of electron transfer is proportional to the frequency at which donor and acceptor states come to resonance and the probability to transfer an electron between donor and acceptor states at the transition state (i...

To aid studies of molecular evolution and to assist in gene prediction research, we have constructed an Exon-Intron Database (EID) in FASTA format. Currently, the database is derived from GenBank release 112, and it contains 51 289 protein-coding genes (287 209 exons) that harbor introns, along with extensive descriptions of each gene and its DNA and protein sequences, as well as splice motif information. There is 17% redundancy inherited from GenBank-a purge at the 99% identity level reduced the database to 42 460 genes (243 589 exons). We have created subdatabases of genes whose intron positions have been experimentally determined. One such database, constructed by comparing genomic and mRNA sequences, contains 11 242 genes (62 474 exons). A larger database of 22 196 genes (105 595 exons) was constructed by selecting on keywords to eliminate computer-predicted genes. By examining the two nucleotides adjacent to the intron boundary, we infer that there is a 2% rate of errors or other deviations from the standard GTellipsisAG motif in nuclear genes. This criterion can be used to eliminate 4921 genes from the overall database. Various tools are provided to enable generation of user-specific subsets of the EID. The EID distribution can be obtained from http://mcb.harvard.edu/gilbert/EID

We describe the results of a series of theoretical calculations of electron transfer pathways between Trp306 and *FADH. in the Escherichia coli DNA photolyase molecule, using the method of interatomic tunneling currents. It is found that there are two conformationally orthogonal tryptophans, Trp359 and Trp382, between donor and acceptor that play a crucial role in the pathways of the electron transfer process. The pathways depend vitally on the aromaticity of tryptophans and the flavin molecule. The results of this calculation suggest that the major pathway of the electron transfer is due to a set of overlapping orthogonal pi-rings, which starts from the donor Trp306, runs through Trp359 and Trp382, and finally reaches the flavin group of the acceptor complex, FADH.

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In recent years several theoretical methods have been developed for evaluation of the magnitude of electronic coupling between distant donor and acceptor complexes mediated by a protein molecule. Most detailed studies have been carried out within the one-electron tight-binding (extended Hückel) approximation for electronic structure of the protein medium. In this paper different approximate and exact one-electron methods such as perturbation theory, exact diagonalization, and method of tunneling currents are reviewed and results of calculations are compared for three HisX-Ru-modified azurin molecules, where X=122, 124, and 126. These systems have been recently synthesized and studied experimentally by Gray and co-workers. The calculations show that perturbation theory results are in excellent agreement with exact calculations if the symmetry of the zeroth-order wave functions of the donor and acceptor metal ions are chosen correctly. A simple computational procedure for construction of such correct zeroth-order functions is proposed.