Introduction

The emergence of cellular life was a central event on the evolutionary pathway from simple organic matter to present-day life forms. In this fundamental step, organic material assembled into boundary structures which acquired metabolism and the capabilities to replicate and evolve.

Any direct record of this stage of evolution is lost. At the present time, it seems unlikely that we will be able to recreate its details with a reasonable degree of certainty. This immediately raises the question of how can we reliably study the formation of cellular life and, even further, whether it is at all possible. It has been suggested by Monod [1] that life originated from a series of highly unlikely events. Since specific conditions leading to these events might never be known, one might conclude that the origin of life is not an appropriate subject of scientific inquiry. An alternative view holds that the emergence of life was a reasonably robust event and its main aspects can be understood, although perhaps not in detail, from basic physical and chemical principles, once we account for different, known limitations to this event.

One type of limitation arises from the environmental conditions on the early Earth. A different set of limitations is imposed by our knowledge of the only known successful ``experiment'' in the origin of life -- the living cell. We require that the earliest precursors of cells -- protocells -- were capable of performing ubiquitous cellular functions, utilizing only those simple molecules which could have existed under prebiotic environmental conditions. We further restrict the processes employed by protocells to those for which a plausible evolutionary pathway into contemporary cellular functions can be postulated. This condition is motivated by the continuity argument [2] that the evolution of cellular structures progressed without undergoing discontinuous transitions.

The assumptions of robustness and continuity are essential for methodological purposes. It is possible that certain steps in the formation of protocells required highly specific environmental conditions the existence of which cannot be proven. It is also possible that protocellular evolution produced dead ends or intermediate structures which left no trace in contemporary cellular functions. However, abandoning the assumptions of robustness and continuity could easily lead to a slippery path of speculations, not amenable to testing. On the other hand, by adhering to these assumptions we can base studies of protocells on the firm foundations formed by our broad knowledge of the structure and functions of contemporary cells.

In this paper we discuss how we can shed light on the functioning of a primitive cell through the application of these concepts in large-scale, molecular-level computer simulations. Computational methods have a unique role in studies of the origin of life. Their goal is to identify the structural and energetic conditions emerging from the fundamental principles of physics and chemistry that successful models of protocellular functions must fulfill [3]. Thus, they establish physico-chemical boundaries for these models which, in turn, provide guidance for laboratory experiments.

In the next section we present the main ideas underlying the concept of the protocell. Then, we briefly describe the computational methods and molecular models used in our studies. The next three sections are devoted to transport of ions across membranes, the formation of proton gradients that can be utilized as an energy source, and the organization of small peptides at membrane interfaces for primitive catalysis. The paper closes with conclusions and suggestions for future research.