J M Kleinberg | PubMed Health

PubMed2001

Are randomly grown graphs really random?

We analyze a minimal model of a growing network. At each time step, a new vertex is added; then, with probability delta, two vertices are chosen uniformly at random and joined by an undirected edge. This process is repeated for t time steps. In the limit of large t, the resulting graph displays surprisingly rich characteristics. In particular, a giant component emerges in an infinite-order phase transition at delta=1/8. At the transition, the average component size jumps discontinuously but remains finite. In contrast, a static random graph with the same degree distribution exhibits a second-order phase transition at delta=1/4, and the average component size diverges there. These dramatic differences between grown and static random graphs stem from a positive correlation between the degrees of connected vertices in the grown graph-older vertices tend to have higher degree, and to link with other high-degree vertices, merely by virtue of their age. We conclude that grown graphs, however randomly they are constructed, are fundamentally different from their static random graph counterparts.

Journal Article↗

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Efficient algorithms for protein sequence design and the analysis of certain evolutionary fitness landscapes.

Protein sequence design is a natural inverse problem to protein structure prediction: given a target structure in three dimensions, we wish to design an amino acid sequence that is likely fold to it. A model of Sun, Brem, Chan, and Dill casts this problem as an optimization on a space of sequences of hydrophobic (H) and polar (P) monomers; the goal is to find a sequence that achieves a dense hydrophobic core with few solvent-exposed hydrophobic residues. Sun et al. developed a heuristic method to search the space of sequences, without a guarantee of optimality or near-optimality; Hart subsequently raised the computational tractability of constructing an optimal sequence in this model as an open question. Here we resolve this question by providing an efficient algorithm to construct optimal sequences; our algorithm has a polynomial running time, and performs very efficiently in practice. We illustrate the implementation of our method on structures drawn from the Protein Data Bank. We also consider extensions of the model to larger amino acid alphabets, as a way to overcome the limitations of the binary H/P alphabet. We show that for a natural class of arbitrarily large alphabets, it remains possible to design optimal sequences efficiently. Finally, we analyze some of the consequences of this sequence design model for the study of evolutionary fitness landscapes. A given target structure may have many sequences that are optimal in the model of Sun et al.; following a notion raised by the work of J. Maynard Smith, we can ask whether these optimal sequences are "connected" by successive point mutations. We provide a polynomial-time algorithm to decide this connectedness property, relative to a given target structure. We develop the algorithm by first solving an analogous problem expressed in terms of submodular functions, a fundamental object of study in combinatorial optimization.

Algorithms↗