VMD and Exploring Forces Behind Protein Folding

Form and function is an important algorithm when it comes to molecular interactions. What is aimed here was a naive attempt to understand the great folding and coding pattern of nature in scale of molecules and atoms. Objectives of this experiment are exploring Visual Molecular Dynamics (VMD) which is an open source software that is used in visualizing, simulating and analysing molecular dynamics and observing the secondary structures of proteins with the bonds that are responsible for folding and acquiring  the accurate form of biological molecules.

Fig. 1 – Tryptophane in the middle with hydrophobic attractions and salt bridge.

Tryptophan Cage: It consists of 20 aminoacids  and in the image charge-charge and hydrophobic interactions can be observed. Whites are hydrophobic and greens are hydrophilic molecules along with the blue represents basic and the red represents acidic ones which cause charge-charge interactions (salt bridges).

Experimental Procedure


The structure has an alpha helix, a loop and unorganized structure. Molecules are not static but dynamic in nature, therefore how the dynamics of Tcage is affected by different environmental conditions has been analysed by using VMD and molecular motion data previously provided.


Dynamics of Tcage is observed under three different conditions;

  • A. constant temperature of 27 C
  • B. heating from 27 C to 100 C
  • C. constant temperature of 37 C, denaturing

Fig. 2 – pink: alpha helix, blue: loop, white: unorganized

Fig. 5 – HB details

We can say that the structure did not change considerably. At a constant temperture of 27C, the mobile part is the unorganized part of the structure. Alpha helix and loop structures maintained their forms however unorganized part which was tied to tryptophane with hydrophobic attractions and a hydrogen bond between one hydrogen of Tryptophane and one oxygen of Arginine is broken in the peak of graphic. This can be identified as “key HB” for this case. Salt bridge which stays at the end of alpha helix structure also remained the same.

When Tcage was heated from 27C to 100 C, the beginning of Alpha helix began to deform. HB and salt bridges were mostly broken, alpha helix and loop structures slowly disintegrated whereas the peptide bonds stayed. HB were the first ones that began to break and they were followed by salt bridges. It lost its circular form and became linear. We can say that, HB, salt bridges and hydrophobic attractions which were responsible for folding in this case are much weaker than the peptide bonds when heated. The protein started to loose its form and therefore its function which is closely related to its secondary structure.

Although the shape looks like Tcage at indicated point because of the unorganized structure folding, the protein was not caging the tryptophane molecule as it can be observed in the right half of Fig.7 as the big white molecule. HB were decreasing in number as the structure was denaturing. However, when it came to the end, the alpha helix structure began to form again. Since environment was at a constant degree, we may say if the conditions are convenient, proteins are tend to fold and molecules come together even after they denaturated.

Large biological molecules are dynamic in water and so in cells and they always explore different forms and affirmations to fold and acquire a function. Some bonds are strong such as peptide bonds that hold aminoacids together while some others are weaker such as hydrogen bonds. Hydrophobic molecules are tend to gather and hide themselves from water mostly in the middle of the structure, while hydrophilic ones are tend to place themselves on sidechains of aminoacids. Salt bridges which are formed between acids and basics are another bond which is also responsible from folding like in the example of Lysine and Aspartic Acid.