Python Programming for Biology: Bioinformatics and Beyond

An introduction to 3D structures of bio-molecules

So far in this book the more biological chapters have focussed on sequences: a linear and

effectively  one-dimensional  representation  of  biological  macromolecules.  Studying

sequences allows us to study the flow of biological information from the genome and how

DNA,  RNA  and  protein  macromolecules  evolve.  However,  this  representation  is

somewhat  removed  from  the  physical  reality  of  the  biochemical  soup  of  life,  which  of

course occurs in three-dimensional space. We can even think in terms of four dimensions,

if you consider time and how things change. Naturally, change in biological molecules is

---

at  the  core  of  all  life  processes;  nothing  stands  still.  Here  we  will  keep  things  relatively

simple, however, and will not delve into the time-dependent, dynamic aspects. Hence, this

chapter simply relates to the three-dimensional arrangements of biological molecules.

Here our primary focus is on the structure of proteins and RNA. This is not to say that

the  structure  of  DNA  is  not  important,  it  is  of  course  vital,  but  the  difference  is  that  for

proteins (and directly functional, untranslated RNA) our understanding of the way biology

works is so much more dependent on a precise three-dimensional structure. DNA, with its

double  helix,  is  necessarily  an  inert  and  repetitive  structure.  Things  happen  to  cause

deviations  from  this  regularity  when  DNA  is  activated  and  deactivated  (for  reading),

transcribed into mRNA, replicated, repaired etc., but it is the proteins of the cell that are

the causal agents for these specific events. The way that proteins interact with DNA is just

one of a plethora of different actions they perform to create the life-sustaining processes

within organisms. The ability of an organism’s proteins to do a multitude of, usually very

precise,  jobs  stems  from  the  fact  that  different  proteins,  encoded  in  different  gene

transcripts,

1

have different sequences of amino acid residues. The combinations of amino

acids cause the different protein chains, initially made in a linear way, to fold into different

three-dimensional  structures.  It  is  the  precision  of  the  various  protein  structures,  i.e.  that

the  same  amino  acid  sequence  virtually  always  gives  the  same  three-dimensional

arrangement  of  atoms,  which  allows  proteins  to  perform  a  task  and  evolve  according  to

this  task,  albeit  catalysing  a  chemical  reaction,  interacting  with  another  biological

molecule or whatever.

Studying the structures of proteins, and the occasional non-translated RNA, allows us to

work out how they operate; what their molecular mechanics are. This not only improves

our understanding for its own sake, but also allows us to intervene in biology at an atomic

level,  as  we  do  when  we  make  new  medicines  and  pesticides  etc.  For  medicine  in

particular, the ability to say why things happen at this very small scale has allowed us to

design  new  compounds  to  affect  biology  in  a  knowledgeable  way,  to  cure  an  ailment  or

disease.  Before  we  had  such  precise  atomic  knowledge  the  best  we  could  do  was  test  a

vast array of existing compounds, just in case one of them had a desirable effect.